Premarketing notification requirements

The Sixth Amendment s premarket notification requirements differ markedly from TSCA in three important respects. First, new substances in the EEC always will be considered "new" under the Sixth Amendment, because the notification requirements are person-specific — i.e. when one company submits a PMN for a particular substance, this does not relieve any other company from the requirement to submit its own PMN before that second company may place the same substance on the EEC market.(J3) Second, the Directive includes a scheme for regular follow-up reporting on the commercial development of new substances, with progressively more extensive (and expensive) testing requirements. Finally, the Sixth Amendment creates a one-time notification for each company (for each new substance), throughout the EEC. Thus, once a Member State has completed its review of a company s PMN (without taking any action to require further testing or to impose limitations upon production or use), that company is not required to provide a PMN to any other EEC country in which it subsequently markets the substance.(9)... 

The U.S. premanufacture notification (PMN) requirements have been in effect for approximately three years, and more than 1250 PMN s have been submitted to EPA. The EEC s premarket notification requirements took effect in September 1981,... 

Many countries have adopted chemical substance iaventories ia order to monitor use and evaluate exposure potential and consequences. In the case of essential oils used in many fragrance appHcations, these oils must be on many of these Hsts. New essential oils used in fragrances are subject to premanufactuting or premarketing notification (PMN). PMN requirements vary by country and predicted volume of production. They require assessment of environmental and human health-related properties, and reporting results to designated governmental authorities. 

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. 

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. 

The Safe Medical Devices Act of 1990, a major revision to the 1976 amendments, among other revised requirements provided two major mechanisms for bringing an IVD medical device to market premarket notification and premarket approval. The act is administered by the FDA s Center for Devices and Radiological Health, of which the Division of Clinical Laboratory Devices (DCLD) is a part. The premarket notification process is used for devices that can be classified... 

The premarket notification application, 510(k), is reviewed by the FDA scientific staff. This evaluation takes into consideration tumor-associated analytes, test requirements, medical usefulness of the test system for a particular clinical claim, and its application (i.e., monitoring or treatment follow-up). The FDA determines the appropriate performance requirements for each tumor analyte category. The agency s staff considers factors, such as consequences of a false positive or false negative, and the importance or impact of an absolute versus a significant change in the results or values of the tumor marker tests. The performance criteria (parameters) of a particular tumor marker test are compared with those of previously... 

Persons and Activities Covered. TSCA 5 creates a premanufacture notification program, whereas the Sixth Amendment requires the submittal of premarket notifications. Thus, U.S. PMN s must be submitted no later than 90 days prior to the completion of R D activities, unless EPA grants permission to produce limited amounts for test marketing purposes. In contrast, companies in... 

Because the Sixth Amendment itself exempts most of the chemicals that are subject to EPA s current rulemaking, In general the Commission does not need to commence any exemption activities analogous to EPA s efforts. Thus, the EEC s premarket program covers only those new polymers that contain 2% or more of a monomer(s). (Any new monomer iis subject to the notification requirements.) Further, because PMN s must be submitted only for new substances that are "placed on the [Community] market," the EEC s PMN requirements generally do not apply to the manufacture and use of intermediates (or of any other new substances, for that matter) by one company at one site.(13)... 

The second major change enacted under the 1962 amendment was the change in the approval process from premarket notification to a premarket approval system. Under the terms of the 1938 law, an NDA would take elfect automatically if the FDA did not respond. For example, the only reason thalidomide was not approved was because Dr. Kelsey returned the application to the sponsor with a request for more information. In contrast, the 1962 law required affirmative FDA action before a drug could be put on the market. Under the terms of the 1962 amendments, the FDA was also empowered to withdraw NDA approval and remove the drug from the market for a variety of reasons, including new evidence that the product was unsafe or that the sponsor had misrepresented or under-reported data. 

As a result of DSHEA, botanical supplements are presumed safe by virtue of being grandfathered by the FDA if the product was marketed before October 15, 1994. Products brought to market after that date only require 75-day premarket notification to the FDA with information that substantiates that the ingredients will reasonably be expected to be safe (65). FDA cannot take action until patients are injured but it is increasingly clear relatively rare adverse events may not be detected until a significant number of patients are killed or injured. 

Medical devices were first made subject to FDA regulation under the FD C Act of 1938. At that time, the statute included no requirement for premarket testing or approval. Congress enacted the Medical Device Amendments of 1976 to require premarket notification for all medical devices, and premarket approval for some old and new devices for which there is no adequate assurance of safety and effectiveness. The 1976 Amendments established a broad new array of statutory requirements and enforcement provisions. This new regulatory approach was supplemented by the Safe Medical Devices Act of 1990 and further refined by the Medical Device Amendments of 1992 and the Food and Drug Administration Modernization Act of 1997. ... 

There is the long-standing belief that the approval process for medical devices is much faster than the IND/NDA drug method. This is certainly true for Class I, Class II, and some preenactment Class III devices—products that can be cleared through Premarket Notification or 510 (k) submissions. Such products are often approved for commercialization in 90 days or less. However, the difference in time is less apparent for manufacturers of new Class III products, where preclinical studies, clinical trials, and the premarket approval process is required. Statistics with respect to time of inception through time to market for new Class III devices are not readily available, but in the author s opinion it would be similar to that required for a new drug. 

A postamendment device is one that was first distributed commercially on or after May 28, 1976. Postamendment devices that the FDA determines are substantially equivalent to preamendment device Class III devices are subject to the same requirements as the preamendment devices. The FDA determines substantial equivalence after reviewing an applicant s premarket notification 510(k). Postamendment devices determined by the FDA to be not substantially equivalent to either pre- or postamendment devices classified into Class I or II are new devices and fall automatically into Class III. Before such devices can be marketed, they must have an approved premarket approval application or be reclassified into Class I or II. 

CDRH approves medical devices through the premarket notification and premarket approval processes. Most marketed devices are approved by the FDA via submission of a Premarket Notification or 510(k). A 510(k) notification is required for Class I devices that are not exempt from notification, all Class II devices, and certain Class III devices. A 510(k) is a premarketing submission demonstrating that the device to be marketed is substantially equivalent to, or as safe and effective as, a legally marketed device that is not subject to premarket approval. The legally marketed, comparator device is termed the predicate device. 

Center for Devices and Radiological Health. Premarket notification 510(k) regulatory requirements for medical devices, August 1995. 

Recent legislation in the U.S.A., the Safe Medical Devices Act of 1990, has increased the range of types of devices required to go through the premarket approval process rather than the premarket notification (510k) process. This may be indicative of future FDA activity in the devices sector along the lines seen with pharmaceutical products. 

New devices. As part of the General Controls requirements, the FDA must be notified prior to marketing any new (or modifying an existing) device for patient use. This premarket notification, called the 510(k) process after the relevant section in the Medical Device Amendments Act, allows the FDA to review the device for safety and efltcacy. 

There are two broad categories that a device can fall into. A device that was marketed prior to May 28, 1976 (the date that the Medical Device Amendments became effective) can continue to be sold. Also, a product that is substantially equivalent to a preamendment device can Ukewise be marketed. However, the FDA may require a premarket approval application for any Class III device (see below). Thus, these preamendment devices and their equivalents are approved by grandfathering. (Premarket notification to the FDA is still required to assure safety and efficacy.) Of course, the question of substantial equivalency is open to an infinite munber of interpretations. From the manufacturer s perspective, such a designation allows marketing the device without a much more laborious and expensive premarket approval process. 

As summarized by the FDA, an investigational device exemption (IDE) allows a device to be used in a clinical study to collect safety and effectiveness data required to support a PMA application or a Premarket Notification [510(k)j submission to FDA. All clinical evaluations of investigational devices must have an approved IDE before a clinical study can be initiated. An approved IDE permits a device to be shipped lawfully for the purpose of conducting investigations of the device without complying with other requirements of the Eood, Drug, and Cosmetic Act that would apply to devices in commercial distribution (FDA, 2009). 

Most new medical devices must undergo a process of premarket notification. Certain Class I devices (see the FDA Web site at www.fda.gov) are exempt from this requirement. There ate certain respiratory-related devices in the list of Class I devices, but, in general, they are ancillary to respiratory diagnostic measurement and health care. 

The FDA will allow manufacturers to change sources of silicone elastomers (and others) if they can show that the replacement material is not substantially different from materials described in existing approved applications. The device manufacturer is still required to certify that the processes of fabrication, cure and sterilization it uses in the manufacture of its device are appropriate for the new material and that the device will perform as intended. Premarket notification submission under section 510(k) of the Federal Food, Drug, and Cosmetic Act (21 USC 360(k) and 21 CFR 807.81(a)(3)(i), or a supplemental premarket approval application under 21 USC 360(k) section 515 and 21 CFR 814.39 is necessary when change could significantly affect the safety or effectiveness of the device. These submissions are required to be submitted and approved before the device may be marketed with the change. 

Standards can have a restrictive effect on new materials as well. The FDA now requires that if a company cites a standard in its premarket notification, a Form 3654 must be completed, which is intended to detail to the Agency the extent to which the standard was applied. The form can be a grueling exercise if not considered at the beginning of letting the contract for testing or if the impact it may have on the submission is not properly understood. The form must include details of any adaptation of the standard to the device under review, deviations from the standards, requirements not applicable to the device, and the name and address of the test laboratory or certification body involved in assessment of conformance to this standard. If this information is not present in the laboratory report, the applicant must provide the information as an attachment to the form for each standard cited. For many standards, completing this form has become an onerous task. Unfortunately, without this level of disclosure, it can be difficult for the FDA to understand the degree to which the biotextile conforms to the claimed standard. Because such standards citations can become product claims of performance, such detailed information is necessary. 

To determine the safety and efficacy of the biotextile implant as required by regulatory authorities such as Food and Drug Administration (FDA) and its need for either premarket approval (PMA) or premarket notification (510k). 

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