An FDA Form 483 is issued to firm management at the conclusion of an inspection when an investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts. FDA investigators are trained to ensure that each observation noted on the FDA Form 483 is clear, specific and significant. Observations are made when in the investigator’s judgment, conditions or practices observed would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.
A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed device (21 CFR 807.92(a)(3)) that is not subject to PMA. Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalency claims.
Section 513(g) governs requests to FDA “for information respecting the class in which a device has been classified or the requirements applicable to a device under [the] Act.”
Medical devices are subject to the adulteration provisions of the FD&C Act under Section 501. A device is held to be adulterated if it includes any filthy, putrid, or decomposed substance, or if it is prepared, packed, or held under unsanitary conditions. The FD&C Act further states that a device is held to be adulterated if: Its container is composed, in whole or part, of any poisonous or deleterious substance; It contains, for the purposes of coloring only, an unsafe color additive; and Its strength differs from, or its purity or quality falls below, that which it claims to represent.
Manufactures a finished device to another establishment’s specifications.
Provides a sterilization service for another establishment’s devices.
Corrective and Preventive Action (CAPA)
The purpose of the corrective and preventive action subsystem is to collect information, analyze information, identify and investigate product and quality problems, and take appropriate and effective corrective and/or preventive action to prevent their recurrence. Verifying or validating corrective and preventive actions, communicating corrective and preventive action activities to responsible people, providing relevant information for management review, and documenting these activities are essential in dealing effectively with product and quality problems, preventing their recurrence, and preventing or minimizing device failures. One of the most important quality system elements is the corrective and preventive action subsystem.
action to eliminate the cause of a detected nonconformity or other undesirable situation. 1. There can be more than one cause for a nonconformity. 2. Corrective action is taken to prevent recurrence. 3. There is a difference between correction and corrective action.
Center for Devices and Radiological Health (CDRH)
has the responsibility for protecting and promoting the public health through the approval of safe and effective medical devices.
Clinical Trials are conducted to allow safety and efficacy data to be collected for health interventions (e.g., drugs, diagnostics, devices, therapy protocols). These trials can take place only after satisfactory information has been gathered on the quality of the non-clinical safety, and Health Authority/Ethics Committee approval is granted in the country where the trial is taking place.
an online registry of clinical trials that are being conducted around the world. ClinicalTrials.gov is operated by the National Library of Medicine at the National Institutes of Health and can be accessed by anyone who has access to the internet.
Any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is released for distribution. 21 CFR 820.3(b)
Data Monitoring Committee (DMC)
An independent committee that may be established by the sponsor to assess, at intervals, the progress of a clinical investigation, the safety data, or the critical performance endpoints and make recommendations to the sponsor whether to continue, modify, or stop an investigation.
De Novo Classification
The De Novo classification pathway under section 513(f)(2) of the FD&C Act, establishing an alternate pathway to classify new devices into Class I or II that had automatically been placed in Class III after receiving a Not Substantially Equivalent (NSE) determination in response to a 510(k) submission. In this process, a sponsor who receives an NSE determination may, within 30 days of receiving notice of the NSE determination, request FDA to make a risk-based classification of the device under section 513(a)(1) of the Act.
All manufacturers (including specification developers) of Class II and III devices and select Class I devices are required to follow design controls [§820.30] during the development of their device. The design control requirements are basic controls needed to ensure that the device being designed will perform as intended when produced for commercial distribution.
Device History File – (DHF)
a compilation of records which describes the design history of a finished device.
Device History Record (DHR)
a compilation of records containing the production history of a finished device.
Device master record (DMR)
a compilation of records containing the procedures and specifications for a finished device.
FDA requires in in Section 510 that manufacturers and other specified processors of devices register their establishments with the FDA and provide to the FDA a list of all devices manufactured in any establishment which they operate. Repackers, relabelers, and importers are also required to register with the FDA.
also called “compassionate use,” provides a pathway for patients to gain access to investigational drugs, biologics and medical devices for serious diseases or conditions. Investigational drugs and devices have not yet been approved by the FDA and they have not been proven to be safe and effective. Therefore, they may be effective in the treatment of a condition, or they may not. It is important to remember that the drug/biologic/medical device may have unexpected serious side effects and that patients need to consider all the possible risks when seeking access to an investigational medical product.
FDA Adverse Event Reporting System (FAERS)
is a computerized database containing reports of adverse events. It supports FDA’s post-market safety surveillance program for all approved drugs and therapeutic biologics.
FDASIA Section 907
directed FDA to report on the extent to which demographic subgroups (sex, age, race and ethnicity) participate in clinical trials in marketing applications for drugs, biologics, and devices. This report provided an important opportunity to take a closer look at the inclusion and analysis of demographic subgroups.
any device or accessory to any device that is suitable for use or capable of functioning, whether or not it is packaged, labeled or sterilized.
Exports or offers for export to the United States (U.S.), a device manufactured, prepared, propagated, compounded, or processed in a foreign country, including devices originally manufactured in the United States. A foreign exporter must have an established address outside the U.S.
Global Harmonization Task Force (GHTF)
encourages convergence at the global level in the evolution of regulatory systems for Medical Devices in order to facilitate trade whilst preserving the right of participating members to address the protection of public health by regulatory means considered to be most suitable. This is achieved by identifying and developing areas of international co-operation in order to facilitate progressive reduction of technical and regulatory differences in systems established to regulate medical devices.
Good Manufacturing Practices (GMP)
current GMP requirements for medical devices are incorporated into a quality system regulation. The quality system regulation includes requirements related to the methods used in, and the facilities and controls used for, designing, manufacturing, packaging, labeling, storing, installing, and servicing of medical devices intended for human use. This action is necessary to add preproduction design controls and to achieve consistency with quality system requirements worldwide. This regulation sets forth the framework for device manufacturers to follow and gives them greater flexibility in achieving quality requirements.
Any importer who furthers the marketing of a device from a foreign manufacturer to the person who makes final delivery or sale of the device to the ultimate consumer or user, but does not repackage, or otherwise change the container, wrapper, or labeling of the device or device package. The initial importer must have a physical address in the United States staffed by individuals responsible for ensuring the compliance of imported devices with all applicable FDA laws and regulations.
Institutional Review Board
As defined in the Code of Federal Regulations Title 21 Part 56 means any board, committee, or other groups formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects.
Investigational Device Exemption (IDE)
An IDE allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data. 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.
Institutional Review Board (IRB)
Any board, committee, or other groups formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of, biomedical research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects. Also known as Ethics Committee (EC).
A person responsible for the conduct of the clinical trial at the trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the Principal Investigator (PI).
International Organization for Standards (ISO)
a panel of global experts who represent various organizations who are involved in establishing and setting the requirements and operating standards for a number of different subject areas. The ISO Standard numbers are what is commonly referenced, such as ISO 9001 – Quality System Standards…
management system for design and manufacture of medical devices.
risk management system for medical devices which determine safety during the product life cycle.
requirements for quality management systems.
In Vitro Diagnostic (IVD)
n vitro diagnostics are tests that can detect diseases, conditions, or infections. Some tests are used in a laboratory or other health professional settings and other tests are for consumers to use at home.
any person who designs, manufactures, fabricates, assembles, or processes a finished device. Manufacturer includes but is not limited to those who perform the functions of contract sterilization, installation, relabeling, remanufacturing, repacking, or specification development, and initial distributors of foreign entities. Makes by chemical, physical, biological, or other procedures, any article that meets the definition of “device” in Section 201(h) of the Federal Food, Drug, and Cosmetic (FD&C) Act.
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 Pharmacopeia, 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 its primary intended purposes. The term ‘device’ does not include software functions excluded pursuant to section 520(o).
Medical Device Manufacturer’s Association (MDMA)
The MDMA is a national trade association based in Washington, DC providing educational and advocacy assistance to innovative and entrepreneurial medical technology companies.
Medical Device Report (MDR)
A report submitted to the FDA by a manufacturer, a physician, or a patient about a marketed device that may have caused or contributed to a death or serious injury.
Medical Device User Fee and Modernization Act of 2002 (MDUFMA)
FDA initiated a Medical Device user fee to support prompt approval and clearance of safe and effective devices. The funds collected serve public health by augmenting the resources of FDA that are devoted to the process for the review of devices and the assurance of device safety and effectiveness so that statutorily mandated deadlines may be met.
MedWatch is FDA’s safety information and adverse event reporting program. It provides important and timely medical product information to healthcare professionals, including information on prescription and over-the-counter drugs, biologics, medical devices, and special nutritional products. Healthcare professionals and consumers can also report serious problems they suspect are related to certain FDA-regulated products.
The misbranding provisions of the FD&C Act in Section 502 cover various aspects of drug and device labeling requirements. Many of the provisions apply to drugs and devices both; however, there are also specific misbranding provisions that apply to only drugs or only devices.
Section 502 of the Federal Food, Drug and Cosmetic Act (FFDCA) contains provisions on misbranding including some that relate to false or misleading labeling. A device’s labeling misbrands the product if:
- Its labeling is false or misleading in any particular;
- It is in package form and its label fails to contain the name and place of business of the manufacturer, packer, or distributor and an accurate statement of the quantity of the contents in terms of weight, measure, or numerical count;
- Any required wording is not prominently displayed as compared with other wording on the device, or is not clearly stated;
- Its label does not bear adequate directions for use including warnings against use in certain pathological conditions or by children where its use may be dangerous in health or against unsafe dosage, or methods, or duration of administration or application;
- It is dangerous to health when used in the dosage or manner or with the frequency or duration prescribed, recommended or suggested in the labeling; or
- It does not comply with the color additives provisions listed under Section 706 of the FFDCA;
- The device’s established name (if it has one), its name in an official compendium, or any common or usual name is not prominently printed in type at least half as large as that used for any proprietary name;
- The establishment is not registered with FDA as required by Section 510 of the FFDCA and has not listed the device as required by Section 510(j) of the FFDCA or obtained applicable premarket notification clearance as required by Section 510(k) of the FFDCA;
- The device is subject to a performance standard and it does not bear the labeling prescribed in that standard;
- There is a failure or refusal to comply with any requirement related to notification and other remedies prescribed under Section 518 of the FFDCA, if there is a failure to furnish any materials or information required by, or requested by the Secretary pursuant to, Section 519 of the FFDCA, or if there is a failure to furnish materials or information relating to reports and records required by Section 522 of the FFDCA; or
- There is any representation that creates an impression of official approval because of the possession by the firm of an FDA registration number.
the non-fulfillment of a specified requirement. 21 CFR 820.3(q)
National Institutes of Health (NIH)
Part of the U.S. Department of Health and Human Services, NIH is the primary Federal agency for conducting and supporting medical research. NIH scientists investigate ways to prevent disease as well as the causes, treatments, and even cures for common and rare diseases. Composed of 27 Institutes and Centers, NIH provides leadership and financial support to researchers in every state and throughout the world.
National Library of Medicine
The world’s largest biomedical library, the National Library of Medicine (NLM) maintains and makes available a vast print collection and produces electronic information resources on a wide range of topics that are searched billions of times each year by millions of people around the globe. It also supports and conducts research, development, and training in biomedical informatics and health information technology. In addition, the Library coordinates a 6,000-member National Network of Libraries of Medicine that promotes and provides access to health information in communities across the United States.
Patient Engagement Advisory Committee (PEAC)
This advisory committee is a forum for the voice of patients and will be asked to advise on complex issues related to medical devices and their impact on patients. The goal of PEAC is to better understand and integrate patient perspectives into our oversight, to improve communications with patients about benefits, risks, and clinical outcomes related to medical devices, and to identify new approaches, unforeseen risks or barriers, and unintended consequences from the use of medical devices.
Premarket Approval (PMA)
is the FDA process of scientific and regulatory review to evaluate the safety and effectiveness of Class III medical devices. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. Due to the level of risk associated with Class III devices, FDA has determined that general and special controls alone are insufficient to assure the safety and effectiveness of class III devices. Therefore, these devices require a premarket approval (PMA) application under section 515 of the FD&C Act in order to obtain marketing clearance. Please note that some Class III preamendment devices may require a Class III 510(k). PMA is the most stringent type of device marketing application required by FDA.
Premarket Notification (510K)
Section 510(k) of the FD&C Act requires a manufacturer who intends to market a medical device to submit a premarket notification [510(k)] to the Agency at least 90 days before introducing the device onto the market. Premarket approval status is automatic for all devices found to be not substantially equivalent to pre-amendments devices. Based on the information provided in the notification, the Agency must determine whether the new device is substantially equivalent to a device already marketed or if it is not an equivalent device. A non-equivalent device must have an approved premarket approval (PMA) application or be reclassified into Class I or Class II before being marketed. The final determination of whether a device is substantially equivalent or non-equivalent resides with the FDA.
Post-Market Surveillance (PMS)
Medical device manufacturers, as well as other firms involved in the distribution of devices, must follow certain requirements and regulations once devices are on the market. These include such things as tracking systems, reporting of device malfunctions, serious injuries or deaths, and registering the establishments where devices are produced or distributed. Postmarket requirements also include postmarket surveillance studies required under section 522 of the act as well as post-approval studies required at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application.
action to eliminate the cause of a potential nonconformity or other undesirable situation. There can be more than one cause for a potential nonconformity. Preventive action is taken to prevent the occurrence.
a systematic, independent examination of a manufacturer’s quality system that is performed at defined intervals and at sufficient frequency to determine whether both quality system activities and the results of such activities comply with quality system procedures, that these procedures are implemented effectively, and that these procedures are suitable to achieve quality system objectives.
Quality System Regulation (QS)
The QS regulation embraces an “umbrella” approach to the CGMP regulation. FDA does not prescribe in detail how a manufacturer must produce a specific device, rather the QS regulation provides the framework requiring that manufacturers develop and follow procedures and fill in the details that are appropriate to a given device according to the current state-of-the-art manufacturing for that specific device. Manufacturers should use good judgment when developing their quality system and apply those sections of the QS regulation that are applicable to their specific products and operations, 21 CFR 820.5 of the QS regulation. FDA has identified in the QS regulation the essential elements that a quality system shall embody, without prescribing specific ways to establish these elements. Because the QS regulation covers a broad spectrum of devices, production processes, etc., it allows some leeway in the details of quality system elements. It is left to manufacturers to determine the necessity for, or extent of, some quality elements and to develop and implement specific procedures tailored to their particular processes and devices.
is a public authority or government agency responsible for exercising autonomous authority over some area of human activity in a regulatory or supervisory capacity. An independent regulatory agency is a regulatory agency that is independent of other branches or arms of the government. Regulatory agencies deal in the area of administrative law—regulation or rulemaking (codifying and enforcing rules and regulations and imposing supervision or oversight for the benefit of the public at large).
Changes the content of the labeling from that supplied from the original manufacturer for distribution under the establishment’s own name. A relabeler does not include establishments that do not change the original labeling but merely add their own name.
Packages finished devices from bulk or repackages devices made by a manufacturer into different containers (excluding shipping containers).
any person who processes, conditions, renovates, repackages, restores, or does any other act to a finished device that significantly changes the finished device’s performance or safety specifications, or intended use.
Reprocessor of Single-Use Device
Performs remanufacturing operations on a single-use device.
any requirement with which a product, process, service, or other activity must conform.
Develops specifications for a device that is distributed under the establishment’s own name but performs no manufacturing. This includes establishments that, in addition to developing specifications, also arrange for the manufacturing of devices labeled with another establishment’s name by a contract manufacturer.
Clinical trials are sponsored or funded by various organizations or individuals, including physicians, foundations, medical institutions, voluntary groups, and pharmaceutical companies, as well as Federal agencies such as NIH, FDA, the Department of Defense, and the Department of Veterans Affairs.
Summary Technical File (STF)
should document design, safety or performance tolerances and pass/fail the technical requirements, including any criteria. Refer to guidance from GHTF Study Group 3 for more information on design controls, including technical requirements applied to design inputs and outputs. An STF should contain Technical Standards, Medicinal or Biological Substances in Combination with a Medical Device, Country-Specific Regulatory Requirements and Guidance.
Unique device identifier (UDI)
an identifier that adequately identifies a device through its distribution and use by meeting the requirements of 830.20 of this chapter. A unique device identifier is composed of: A device identifier – a mandatory, fixed portion of a UDI that identifies the specific version or model of a device and the labeler of that device; and A production identifier – a conditional, variable portion of a UDI that identifies one or more of the following when included on the label of the device:
- The lot or batch within which a device was manufactured;
- The serial number of a specific device;
- The expiration date of a specific device;
- The date a specific device was manufactured.
- For an HCT/P regulated as a device, the distinct identification code required by 1271.290(c) of this chapter.
Universal product code (UPC)
the product identifier used to identify an item sold at retail in the United States.
Any foreign establishment engaged in the manufacture, preparation, propagation, compounding, or processing of a device imported into the United States must identify a United States agent (U.S. agent) for that establishment. Information about a foreign establishment’s U.S. Agent is submitted electronically using the FDA Unified Registration and Listing System (FURLS system) and is part of the establishment registration process. The U.S. agent identified will be required to complete an automated process to confirm that they have agreed to act as the U.S. agent.
U. S. manufacturer of export only devices
Manufactures medical devices that are not sold in the U.S. and are manufactured solely for export to foreign countries
used to provide assurance that an activity or phase has been completed in an acceptable manner and that the next activity or phase can begin. Encompasses verification and extends the assessment to address whether devices produced in accordance with the design actually satisfy user needs and intended uses.
A warning letter is a communication from FDA regarding violations that must be addressed with confirmation of steps taken confirmed in writing to the agency.