Substantial equivalence

Two statutory provisions of Tide 21 govern the introduction of new medical devices into the marketplace. Section 515 estabHshes a premarket approval appHcation (PMA) containing data and information demonstrating the safety and effectiveness of a device. Section 510(k) estabHshes a premarket notification process. Under this process, a manufacturer is required to file with the EDA, 90 days before a new device is to be marketed, a premarket notification demonstrating that the device in question is substantially equivalent to a device that was on the market before enactment of the 1976 Amendment and therefore marketable without formal EDA approval. 

Post-amendment devices ate automatically classified as Class III devices. However, a post-amendment device can be brought to market under the 510(k) process, if the PDA determines that the device is "substantially equivalent" to a preamendment device. If the post-amendment device is identical to a preamendment device, it is substantially equivalent. Then the 510(k) is accepted by the PDA and the post-amendment device is placed in the same class as the preamendment device to which it is substantially equivalent. Pot example, a wound dressing identical to a preamendment Class I wound dressing would be found substantially equivalent to the preamendment wound dressing and classified in Class I. 

The Federal Trade Commission has aimounced a rule, effective November 30, 1995, that sets test procedures and labeling standards for recycled oil used as engine lubricating oil (35). The test procedures used are those contained in the Engine Oil Licensing and Certification System of the American Petroleum Institute (API) (36). The rule states in effect that if recycled oils meet the requirements of the API Certification System, such oils ate substantially equivalent to new oil for use as engine oil. This federal rule preempts certain state recycled oil rules (35). 

Unless otherwise exempt, a firm must submit a premarket notification, also called a 510(k), to the PDA 90 days before it intends to market a device for the first time (17). The 510(k) submission must contain sufficient information to show that the device in question is substantially equivalent to a legally marketed device for a particular intended use. This notification is also required for a product when there is a change or modification to a product that may significantly affect the safety or effectiveness of the device, or when there is a significant change or modification to the intended use of the device. 

Class III devices, unless they are substantially equivalent to a device already marketed without a PMA appHcation, require formal PDA approval through the PMA process before initial sale. The PMA process is comparable to the new dmg approval process (18). In both cases, safety and effectiveness data must be reviewed by PDA prior to marketing. An approved PMA appHcation acts like a private Hcense granted to the appHcant to market a particular device. Other firms seeking to market the same type of device for the same use must also have an approved PMA. 

PMA requirements differ between preamendment and post-amendment devices. Preamendment devices are those in commercial distribution before May 28, 1976 post-amendment devices are those first commercially distributed after the date. Class III post-amendment devices that are not substantially equivalent to preamendment Class III devices are considered new devices. Manufacturers of such devices are required to obtain PMA appHcation approval before marketing these. If the post-amendment device is substantially equivalent to a preamendment device and PDA has not initiated a regulatory process specifically requiring the submission of a PMA for the device category, a 510(k) submission can be made. 

Cla.ss II Performance Sta.nda.rds. This category regulates devices for which General Controls are not sufficient to ensure safety and effectiveness. Class 11 controls iaclude all the controls ia Class 1. In addition, manufacturers of sutures ia Class 11 must give the EDA 90-days notice of their iatent to market the suture, by way of a 510(k) filing providing data to show that the suture is "substantially equivalent" to an already-approved device. Most sutures were reclassified iato Class 11 ia 1989. Other than USP standards, performance standards for sutures have not actually been promulgated, but the EDA has taken the stand that sufficient information exists ia the pubHshed Hterature to ensure the safety and effectiveness of sutures ia this class. 

Class III Premarket Approval. Similar to a new dmg approval, a premarket approval grants the appHcant a Hcense to market a specific weU-characterized device. These devices are subject to the requirements of Section 515 of the Eood, Dmg, and Cosmetic Act. A post-amendment device is a device put ia commercial distribution after May 28, 1976. If it is not substantially equivalent to a preamendment device it is automatically ia Class 111, and a premarket approval appHcation (PMA) is required. The appHcation must iaclude reports of preclinical and clinical studies done ia support of claims of safety and efficacy as well as any labeling claims made for the device. Once the PMA is submitted, the PDA determines whether the appHcation iacludes the required information. If the PMA is suitable for scientific review, the PDA has 180 days from the filing date to approve or deny the appHcation. Polybutester, polydioxanone, polyglyconate, and ePTPE sutures are all regulated as Class 111 devices. 

Regulation. Dental implants are regulated by the Food and Dmg Administration. AH dental implants faH iato the FDA class III which covers devices that are life sustaioiag, life supportiag, or are implanted iato the body and have the potential to cause unreasonable risk, illness, or iajury. Devices ia class III are requited to have appHcatioas for premarket approval (315). There are 15 to 20 companies that have FDA marketing clearance for specific dental implants, based on substantial equivalency to implants marketed prior to 1976, and approximately one third of these companies are foreign. Marketing clearance is not the same as premarket approval. 

Both of these approaches have been attempted, and both are substantially equivalent for heterocyclic (e.g. quinoline and isoquinoline) and homocyclic (naphthalene) systems. Consequently, in the subsequent discussion it is fruitful to include the available work on naphthalene derivatives. In the case of the fused six-membered rings, Eq. (3) is not applied because it does not permit treatment of the 5- and 8-positions, and the available series as a whole are too short to make this treatment useful. 

For tanks with a capacity of 20,000 barrels or more, the requirements for the vacuum condition are very close to the theoretically computed value of 2 cubic feet of air per hour per square foot of total shell and roof area. For tanks with a capacity of less than 20.000 barrels, the requirements for the vacuum condition have been based on 1 cubic foot of free air per hour for each barrel of tank capacity. This is substantially equivalent to a mean rate of vapor-space-temperature change of 1(X)F per hour. 

Investigations of devices that have already received FDA-clearance due to the fact that they were already on the market before medical devices were regulated or were shown to be substantially equivalent to one. 

The 510(k) pre-market notification process is not as onerous as the pre-market approval procedure, as clearance to market a device is not based on actual assessment of the safety and effectiveness of the particular device in question. Instead, devices can be cleared on the basis that they are substantially equivalent to existing devices that have been recognised as safe and effective, or that they conform to specific device standards promulgated or recognised by the FDA. There are four procedural variations to the 510(k) notification process. 

If a manufacturer has modified their own device they can avail of a special 510(k) procedure for declaring substantial equivalence to their existing device, provided that the intended use or the basic technology has not changed. They must apply design controls and risk analysis to the development process, but the advantage is that they can receive a faster review process. 

The establishment of performance criteria for a given tumor marker test is not a simple process because accuracy and precision are unique for each type of analyte and its application. Establishing methodological limits for accuracy, precision, sensitivity, and specificity often requires standard reference materials, quality control materials, comparative studies, and actual clinical specimens. Accuracy and precision must be measured over the analyte reportable range for which the device is intended to be used. Sensitivity and specificity must be considered with respect to the intended clinical use of the device. Also, the indications for use should be carefully considered in the design of the study protocol. The indications for class II should be to monitor residual tumor after surgery (or radiation), the recurrence of tumor, or response to therapy. A 510(k) must provide clear evidence that the device is accurate, safe, effective, and substantially equivalent to a device legally marketed in the United States. 

If the resin were insufficiently dried, the moisture present could cause voids within the molded part. This happens when the water evaporates and leaves open spaces. One effect of voids can be a lower bulk density. Bulk density was measured by the displacement method in accordance with ASTM D792 [7], and was found to be substantially equivalent for the two samples, as shown in Table 12. 

When an IVD is developed as a kit or system to be used with specific equipment and is sold to multiple laboratories, it is considered a device in interstate commerce and is subject to premarket review. When the IVD is a novel test, premarket approval (PMA) will be based on the analytical and clinical validation that will determine whether the test is safe and effective for clinical use. When there is evidence that the IVD is substantially equivalent to a legally marketed device, FDA clears such tests under section 510(k) of the Device Amendments to the Food, Drug and Cosmetic Act. The necessary level of evidence and requirements are described in more detail below. 

Under the Medical Device Amendments of 1976, the FDA is responsible for premarket evaluation of all laboratory testing devices (in vitro diagnostics) intended to be commercially marketed in the United States. There are two major pathways for introducing a medical device into the marketplace the premarket notification [510(k) clearance] and the premarket approval (PMA). The purpose of the 510(k) is to establish that a device is substantially equivalent (SE) to a legally marketed (predicate) device. The purpose of the PMA evaluation process is to establish the intrinsic safety and effectiveness of a new device. Unless specifically exempt, a sponsor must have an approved PMA or cleared premarket notification [510(k)] by the FDA before a device may be legally marketed for IVD use (Fig. 1). 

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