Excerpt from Special Edition: Medical Device Compliance -- The 510(k) - Its Purpose, Compilation, and Submission

Medical device companies must, by law, meet certain requirements before marketing a new or substantially modified (physically or in labeled/intended use) device. For any device, except the most benign (generally Class I) or the newest technology (generally Class III), this means the manufacturer or specification developer must seek regulatory clearance for any new or substantially changed device prior to marketing by means of a Premarket Notification, or 510(k), submission. History Medical products manufactured in the United States for sale in the U.S., or manufactured outside the U.S. and shipped into the U.S. for sale in the U.S., and meeting the definition of a device under section 201(h) of the Federal Food, Drug and Cosmetic Act (FD&C Act, or "the Act") are regulated by the U. S. Food and Drug Administration (FDA). Medical devices are subject to general controls and other controls in the FD&C Act. General controls of the FD&C Act are the baseline requirements that apply to all medical device manufacturers. Unless specifically exempted, medical devices must be: Properly labeled and packaged; Cleared for marketing by the FDA; Consistent in meeting their labeling (intended use) claims; and Manufactured under GMPs (Good Manufacturing Practices, now known as the new Quality System Regulation, a mandated quality assurance system). The FDA regulates devices to assure their safety and effectiveness. To fulfill provisions of the Act, FDA develops and promulgates rules to regulate devices intended for human use. These rules regulate various aspects of the design, clinical evaluation (where required), manufacturing, packaging, labeling (including promotional information), commercial distribution, and postmarket surveillance of devices. These regulations are published in the Federal Register. Final regulations are codified annually in the Code of Federal Regulations (CFR). Most device regulations are in Title 21 CFR Parts 800 to 1299. The definition of a device appears in section 201(h) of the Act (not the CFR). A device is "...an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component, part, or accessory, which is: Recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them, 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 Intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of 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 primary intended purposes…" Certain components such as blood tubing sets, major diagnostic X-ray components, and stand-alone software are regulated by the FDA as finished devices because they are accessories to finished devices and meet the above definition of a device. Software that is to be marketed to enhance the performance of a device is regulated as an accessory to the device that poses the greatest risk to the patient. For example, software used with a Class III device may be regulated as Class III. The manufacturer of accessories is subject to the medical device regulations when the accessory is labeled and marketed separately from the primary device for a health-related purpose to a hospital, physician, or other end-user. As mentioned in the opening, the FDA has established classifications for the different generic types of devices, based on the risk to the population. Hence, the level of control necessary to assure the safety and effectiveness varies with the class of the device. The three classes and the requirements which apply to them are: Class I General Controls (GMPs); Class II General Controls and Special Controls; Class III General Controls and Premarket Approval (PMA). General controls, which apply to all medical devices, include: Prohibition of adulteration, section 501 of the Act; Prohibition of misbranding, section 502 of the Act; Banned devices, section 516 of the Act; Notification; and repair, replacement or refund; section 518 of the Act; Records and reports, section 519 of the Act; and Restricted devices; section 520 of the Act. General controls contain requirements for device manufacturers or other designated individuals to: Register their establishment with the FDA (Form FDA 2891); List their devices with FDA (form FDA 2892); Comply with labeling regulation (21 CFR Part 801, 809, or 812); Submit a premarket notification, 510(k), to FDA; and Design and produce devices under good manufacturing practices (GMPs), now designated the Quality System Regulation (QS Regulation; 21 CFR Part 820). In order to market a medical device in the U.S., manufacturers must go through one of two evaluation processes: Premarket notification [510(k)], unless exempt, or premarket approval (PMA), a much more involved process. Most medical devices are cleared for commercial distribution in the U.S. by the premarket notification [510(k)] process. In certain instances, devices legally on the market prior to May 28, 1976, may not require either a 510(k) or PMA submission. This exclusion does NOT apply to a "me-too" device, newly manufactured by another company, but only to those devices marketed prior to 1976 and still being marketed by the same company while basically unchanged. The Medical Device Amendments of 1976 mandated the submission of a premarket notification [510(k)] to the FDA. The purpose of a 510(k) is to demonstrate that the medical device to be marketed is substantially equivalent (SE) to a legally marketed device that was or is currently on the U.S. market. Predicate Device Proving SE requires the location/identification of a predicate device. A predicate device is a device that: Was legally marketed in the U.S. prior to May 28, 1976 (preamendment; "grand-fathered" devices), and: Has not been significantly changed/ modified since then; and For which a regulation requiring a PMA application has not been published by the FDA; or Which has been reclassified from Class III to Class II; or Which itself has been found to be substantially equivalent through the 510(k) process, after May 28, 1976. The term predicate device only applies to devices in categories subject to 510(k) review, and not devices requiring premarket approval (PMA), since the basis of the PMA is not a comparison of one device to another (preexisting device) as it is in a 510(k). Substantial Equivalence (SE) A device is SE if, in comparison to a legally marketed (predicate) device, it has the: Same intended use as a predicate, and Same technological characteristics as the predicate device; or has the: Same intended use as a predicate; and Different technological characteristics, and the information submitted to FDA: Does not raise new questions of safety and effectiveness; and Demonstrates that the device is as safe and as effective as the legally marketed device. Different technological characteristics include, but are not limited to, changes in materials, design, energy sources, and principles of operation. A claim of SE does not mean the devices must be identical. SE is established with respect to: intended use, design, energy used or delivered, materials, performance, safety, effectiveness, labeling, biocompatibility, standards, and other applicable characteristics. If the FDA finds the device to be SE, the FDA will send the manufacturer a marketing clearance letter (not an "approval"), referred to as an "SE letter," and the device may be marketed as described in the 510(k). The goal of the FDA is to submit such a finding, if the device is truly SE and the submission is basically complete, in approximately 90 days from date of receipt of the 510(k) submission. Complexity of the device, inaccuracies or omissions in the submission, or similar, can result in delays or a "refuse to accept" of the submission on the part of the FDA. If the FDA finds the device to be NSE (not substantially equivalent), the manufacturer will be so notified. The manufacturer then has the option to: Resubmit another 510(k) with new (not restated) information; or Petition the FDA requesting the device be reclassified into Class I or II, as described in section 513(f) of the Act, if warranted; or Submit a PMA. Manufacturers may not place their device into U.S. commerce until they receive a marketing clearance/SE letter from the FDA. When to Submit According to 21 CFR section 807.81, a pre- market notification submission is required when (see Figure 1, FDA SE Requirements Matrix): A device that requires a 510(k) clearance is planned to be marketed for the first time by a medical device firm who is required to register; or An existing device with 510(k) clearance or a preamendment device is being marketed and is to be changed or modified in a way that could significantly affect its safety or effectiveness, e.g., significant change or modification in design, material, chemical composition, energy source, or manufacturing process; or A major change or modification in the intended use for a preamendment or 510(k) device is claimed (see Changes/Modifications). A submission is not required if the: Device has been exempted by the classification regulations in 21 CFR Parts 862-892. Most Class I devices are exempt (subject to limitations on exemptions); or Device requires a PMA; or Device was legally distributed by the same firm in the U.S. prior to May 28, 1976, provable/documented, i.e., is preamendment/grandfathered; and it has not been significantly changed since then; or Rights to market a preamendment or 510(k) cleared device has been acquired from another firm, and the: Device has not been significantly changed since then; and New owner does not make any changes to the device; or Device is being distributed under a "Private Label," i.e., a preamendment device or a device with a valid 510(k) which is being placed into commercial distribution for the first time by a distributor under its own name or a repackager who places its own name, on a device, provided no changes are made to the device, its indications for use, and it is not further processed, e.g., sterilized, in a manner not dealt with in the existing 510(k)...