Premarket Notification

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. 

Investigational New Drug Applications (INDs), NDAs, Premarket Approval Applications (PMAs), Premarket Notifications (5 lO(k)s), Investigational Device Exemptions (IDEs), Biological Master Files (BMFs) and DMFs that are referenced in the current application. 

Where necessary the manufacturer must carry out, or arrange for, safety testing. Many countries operate mandatory premanufacturing and premarketing notification schemes of which safety testing is the cornerstone. Within the European Community under Directive 67/548/EEC and its sixth amendment 79/831/EEC, Competent Authorities must be... 

Guidance for Industry Premarket Notification (510(k)) Guidance Document for Contact Lens Care Products. Center for Devices and Radiologic Health, FDA, Rockville, MD, 1997. 

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... 

There are five fundamental elements of FDA regulation of medical devices (1) facility registration and product listing (2) safe use of investigational devices (3) premarket notification (unless exempt) and product labeling ... 

This part compares basic provisions of the U.S. premanufacture and the EEC premarket notification programs.(3)... 

Articles 5-8 and Annexes VII and VIII in the Sixth Amendment ) contain the key provisions of the EEC s premarket notification program. Articles 2, 9-13, and 20-23 also are particularly relevant. 

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... 

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)... 

In contrast, as a Directive by the EEC Council to the Member States, the Sixth Amendment is not self-implementing, and it is not directly enforceable against individual companies. Rather, each EEC country must implement its own premarket notification laws, regulations, and administrative provisions. These must be consistent with the overall framework of the Sixth Amendment, and they must not create the types of conflicts or intra-EEC barriers that the Directive was intended to prevent in the first place. Nonetheless, they may be different from one another, to reflect local policies and approaches to specific regulatory matters. 

Followup Reporting and Testing Under the Sixth Amendment. Followup reporting and testing are integral parts of the Sixth Amendment s premarket notification scheme. The Directive itself... 

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,... 

A conflict clearly exists between permanent confidentiality, available under the system of U.S. laws, and the eventual disclosure of identities of specialized chemical substances which had heretofore been undisclosed, but which are now affected by EINECS or by EEC s premarketing notification system. The rules are different the assumptions regarding disclosure are different. Perhaps the best solution a lawyer could offer is that member states should be willing to adjudicate individual cases of specific confidentiality needs. Inventories of existing substances are rules, adopted prospectively to announce to the world both the existence of a material and its regulatory status. Those rules can operate to accommodate both public and private needs. 

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. 

F. Premarket Notification, Investigational Device exemptions including Humanitarian Exemptions, Premarket Approval, Product Development Protocols, Classification, Device Tracking, Petitions for Reclassification, postmarket surveillance under Sections 510(k), 513, 515, 519, 520(g) and (m), and 522, and the advisory committees necessary to support these activities. 

USFDA Premarket Notifications for Food Contact Substances, United States Food and Drug Administration, Washington, DC, June 6, 2000. 

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). 

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. 

Exemption (IDE), New Drug Application (NDA), Abbreviated New Drug Application (ANDA), Biologies License Application (BLA), device premarket notification [510(k)], or device Premarket Approval Application (PM A). 

Abbreviated new drug applications are submitted to gain approval of generic versions of already approved drug products. Premarket notification [510(k)] applications are the mechanisms for marketing medical devices that are substantially equivalent to already marketed device products. Both of these applications are based on approved similar product information. 

Buehler EV (1964) A new method for detecting potential sensitizers using the guinea pig. Toxicol Appl Pharmacol 6 341 Center for Devices and Health (1999) Guidance for Industry and FDA Reviewers/Stuff Premarket notification [510(K)] Submission for Testing for Skin Sensitization to Chemicals in natural Rubber Production. U.S. Department of Health and Human Service, FDA... 

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