PMA Application Methods

A PMA application involves many volumes of material to be submitted to FDA. The volumes include device description and intended use, nonclinical and clinical studies, case report forms, manufacturing methods, labeling, etc.

Required Elements

There is no preprinted form for a PMA Application. Unless an omission is justified by the applicant [§814.20(d)], a PMA must include all of the following:

1. The name and address of the applicant.
2. A table of contents that specifies the volume and page number for each item referred to in the table.
• The PMA must include separate sections on nonclinical laboratory studies and on clinical investigations involving human subjects.
• Six copies of the PMA are required, each bound in one or more numbered volumes of reasonable size. To facilitate review by the advisory committee(s), additional copies may be requested by FDA.
• Trade secret or confidential commercial or financial information must be included in all copies of the PMA. The applicant must identify in at least one copy any information that they believe to be trade secret or confidential commercial or financial information.
3. A summary section in sufficient detail to provide a general understanding of the data and information in the application. Tip: The summary section should contain brief statements of major points found elsewhere in the PMA and should be approximately 10 to 15 pages in length.

The PMA application can be submitted via the following methods:

• Traditional PMA
• Modular PMA
• Product Development Process
• Humanitarian Device Exemption

Traditional PMA

In the traditional PMA method, the complete PMA application is submitted to FDA at once. This method is generally used if the device has already undergone clinical testing and has been approved in a country with established medical device regulations.

Modular PMA

In a Modular PMA the complete contents of a PMA are broken down into well-delineated components (or module) and each component is submitted to FDA as soon as the applicant has completed the module, compiling a complete PMA over time. The PMA is viewed as a compilation of sections or "modules," such as preclinical, clinical, manufacturing that together become a complete application. This method is recommended for products that are in early stages of clinical study. This method is not appropriate when the applicant is very close to being ready to submit a PMA or when the device design is in a state of flux or likely to change.

The process begins with a PMA Shell which lays out the plan for submission of the modules. The shell is an outline of modules and identifies information necessary to support the filing and approval of a specific Class III product through a combined IDE-PMA process. The review team will work with applicants to develop a customized shell for each specific product that includes module contents and suggested timelines. It is developed individually with the manufacturer for a specific device.

FDA reviews each module separately as soon as it is received allowing manufacturers to receive timely feedback during the review process. This may allow more rapid closure when the last components are submitted because much of the review work will have already been done.

Product Development Protocol

In the product development protocol (PDP) method for gaining marketing approval, the clinical evaluation of a device and the development of necessary information for marketing approval are merged into one regulatory mechanism. Ideal candidates for the PDP process are those devices in which the technology is well established in industry. The PDP process provides the manufacturer with the advantage of predictability once the agreement has been reached with FDA.

The PDP allows a sponsor to come to early agreement with FDA as to what would be done to demonstrate the safety and effectiveness of a new device. Early interaction in the development cycle of a device allows a sponsor to address the concerns of the FDA before expensive and time consuming resources are expended.

The PDP is essentially a contract that describes the agreed upon details of design and development activities, the outputs of these activities, and acceptance criteria for these outputs. It establishes reporting milestones that convey important information to the FDA as it is generated, where they can be reviewed and responded to in a timely manner. The sponsor would be able to execute their PDP at their own pace, keeping FDA informed of its progress with these milestone reports. A PDP that has been declared completed by FDA is considered to have an approved PMA (§814.19).

Humanitarian Device Exemption

Humanitarian Use Device (HUD) is a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year. Humanitarian Device Exemption (HDE) is a marketing application for an HUD (Section 520(m) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)). An HDE is exempt from the effectiveness requirements of Sections 514 and 515 of the FD&C Act and is subject to certain profit and use restrictions.