Premarket approval application

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. 

Preload-venous pressure, 5 108 Premanufacture notices (PMNs), 18 542 Premarket Approval Application (PMA), 24 140... 

Class III Premarket Approval. Similar to a new drug approval, a premarket approval grants the applicant a license to market a specific well-characterized device. These devices are subject to the requirements of Section 515 of the Food, Drug, and Cosmetic Act. A post-amendment device is a device put in commercial distribution after May 28, 1976. If it is not substantially equivalent to a preamendment device it is automatically in Class III, and a premarket approval application (PMA) is required. The application must include reports of preclinical and clinical studies done in support of claims of safety and efficacy as well as any labeling claims made for the device. Once the PMA is submitted, the FDA determines whether the application includes the required information. If the PMA is suitable for scientific review, the FDA has 180 days from the filing date to approve or deny the application. Polybutester, polydioxanone, polyglyconate, and ePTFE sutures are all regulated as Class III devices. 

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). 

DRAFT GUIDANCE FOR INDUSTRY AND FDA STAFF-ANNUAL REPORTS FOR APPROVED PREMARKET APPROVAL APPLICATIONS (PMA)3... 

The Medical Device User Fee and Modernization Act (MDUFMA) amended the Federal Food, Drug and Cosmetic Act to provide the FDA with important new responsibilities, resources, and challenges [7]. The MDUFMA has three significant provisions (1) Premarket Approval Applications (PMAs), Product Development Protocols (PDPs), Biological License Applications (BLAs), certain supplements, and 510(k)s are now subject to fees. (2) Establishment inspections may be conducted by... 

Clinical data are required in all premarket approval applications. The PMA applicant must provide a cogent demonstration of the safety and effectiveness for all diagnostic and/or therapeutic medical claims for the device based on laboratory, animal, and clinical data. 

Sponsors shall maintain the records listed above during the investigation and for a period of 2 years after the later of the following two dates the date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a premarket approval application or a notice of completion of a PDP. 

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. 

Figure 2 Original PMA (premarket approval) application review and approval decision process.

Unless the device meets the criteria for a me too product, panel review will be required. Section 512(c)(2) of the act requires that a premarket approval application be referred to an appropriate FDA Advisory Panel for study and for submission of a report and recommendation respecting approval of the application. The definition of a me too device can be found in FDA Guidance P86-6, 7/25/86. 

XXV. AVAILABILITY OF SAFETY AND EFFECTIVENESS SUMMARIES FOR PREMARKET APPROVAL APPLICATIONS... 

Class III. Premarket Approval applies to devices for which general controls do not suffice or for which insufficient information is available to write a performance standard to provide reasonable assurance of safety and effectiveness. Also, devices which are used to support or sustain human life or to prevent impairment of human health, devices implanted in the body, and devices which present a potentially unreasonable risk of illness or injury. New Class III devices, those not substantially equivalent to a device on the market prior to enactment (May 28,1976), must have approved Premarket Approval Applications (Section 510 k). 

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. 

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. 

A new device, that is, one not substantially equivalent to a preamendments device, remains a class III device requiring FDA approval of a premarket approval application (PMA) unless FDA reclassifies it into class I or class II, usually in response to a manfuacturer s petition. In the premarket approval process the manufacturer must establish by valid scientific evidence that the device is safe and effective for its intended use. This evidence is usually data from clinical investigations. 

In the United States, the average cost to bring a product firom concept to clearance was approximately 31 million for a 510(k) application and 94 million for a premarket approval application. 

There are two primary pathways by which the FDA permits a medical device to be marketed premarket clearance by means of a 510(k) notification, or premarket approval by means of a PMA ( Premarket Approval Application ) or PDP ( Product Development Protocol ) submission. 

Guidance for Industry and FDA Staff Class II Special Controls Guidance Document Tissue Adhesive for the Topical Approximation of Skin. Issued May 30, 2008. Supersedes Cyanoacrylate Tissue Adhesive for the Topical Approximation of Skin — Premarket Approval Applications (PMAs), dated February 13, 2004 (issued on July 3, 2007), contact George J. Mattamal, Ph.D., at 240-276-3619 or by email at george.mattamal fda.hhs.gov. 

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