Medical Device and Combination Products Services

Section 513(g) of the FD&C Act provides a means for device manufactures to obtain the agency’s view regarding the classification and regulatory requirements for a device. 513(g) submissions should include information and characteristics of the device and rationale behind why it should fall within a specific class (Class I, Class II, or Class III). Submitted requests will be answered within 60 days of the receipt of a writing request, providing information with respect to the classification of a device and the associated regulations.

The FDA will either:

1. 1. Inform the requester if the product does not meet the requirements for classification as a device, OR
   2. Issue information regarding their assessment of the type and class of the device, any requirements applicable to devices within the particular class, and whether a PMA, 510(k), or neither is required in order to market the devices of the particular class.

FDA does not review data related to substantial equivalence or safety and effectiveness in a 513(g) request, however, the 513(g) mechanism provides a useful resource for device manufacturer to determine the best course of action for their device development.

The Breakthrough Device Program allows for the expedited development and review of certain medical devices and device-led combination products that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.

Upon designation, the FDA ensures that the sponsor receives timely interactive communications to help them design an efficient device program by involving a specialized FDA team including senior management. Moreover, the FDA will allow efficient and flexible clinical trials, when practical and scientifically appropriate, and expedite the review of manufacturing and quality systems compliance. Designation also includes a rolling review to allow the sponsor to use timely post-market data collection, when scientifically appropriate.

Eligibility Criteria:

1. 1. The device must provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions; AND
   2. The device must:

I) represent a breakthrough technology,

II) have no approved or cleared alternatives,

III) offer significant advantages over existing approved or cleared alternatives, OR

IV) demonstrate that its availability is in the best interest of patients.

The de Novo classification is a risk-based classification process by which a novel medical device has general and/or special controls to assure safety and effectiveness for the intended use and there are no predicate devices already on the market.

Granted de Novo requests establish a new classification regulation for a new device type and can serve as predicate devices for 510(k) submissions of future devices of the same type.

Humanitarian Device Exemption (HDE) is a marketing application for an Humanitarian Use Device (HUD). If a medical device is approved under HDE, it becomes exempted from the effectiveness requirements in the HUD application. This exemption was created as a part of the Safe Medical Devices Act of 1990 due to the increasing difficulty of obtaining positive clinical efficacy data from a population size of below 8,000 Americans. However, an HDE has a prohibition put on profits, with only a set Annual Distribution Number (ADN) of devices that can be sold for profit. In addition, an HDE is only eligible to be sold for profit if the device is indented for the treatment or diagnosis of a pediatric disease or condition, a disease or condition that occurs in adults only, or a disease or condition that affects a subset size where development of the device is not feasible or highly impractical.

A Humanitarian Use Device (HUD) is defined as a medical device that is intended to benefit patients in either treatment or diagnosis of a disease that affects or is manifested in not more than 8,000 individuals in the US annually. Similar to Orphan Designation, this program was created to encourage the development of medical devices intended for rare conditions by creating an alternative pathway to market. Devices that wish to apply for Humanitarian Device Exemption (HDE) must first be classified as a Humanitarian Use Device (HUD).

An Investigational Device Exemption (IDE) is an exemption to the FD&C Act that allows for an unapproved device to be used in clinical studies in order to collect data regarding its safety and efficacy. Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k)s require clinical data to support the application. Sponsors may apply for IDE and obtain institutional review board (IRB) approval for the clinical evaluation of a device.

Approved IDEs relieve devices from requirements of the FD&C Act, allowing them to be legally shipped nationwide for the purpose of performing clinical investigations of the device. Sponsors of IDEs are also exempt from the Quality System Regulation except for the requirements for design controls.

Class III medical devices require a PMA, the most stringent type of premarket submission. Before the FDA approves a PMA, the sponsor must provide valid scientific evidence demonstrating reasonable assurances of safety and effectiveness for the device is intended use. PMA’s require 180 days of review time by the FDA.

A 510(k) is a premarket submission made to FDA to demonstrate that the device to be marketed is as safe and effective as a legally marketed device (predicate). Therefore, a 510(k) pathway is reasonable when a sponsor is developing a medical device intended for human use, similar to a predicate device already on the market. The sponsor must include details on the similarities and differences between the devices and that it maintains the same levels of efficacy and intended use as the predicate device, in the application. 510(k)’s require 90 days of review time by the FDA.

A Pre-RFD is intended to be an abbreviated summary of the relevant information for the Office of Combination Products (OCP) to make a preliminary non-binding assessment regarding the regulatory identity or classification of a human medical product as a drug, device, biologic, or combination product. This includes a non-combination or combinations product’s assignment to the appropriate Review Agency Center (CDER, CDRH, or CBER). Pre-RFD processes require a description of how the product achieves its intended therapeutic/diagnostic effect. The FDA will review and provide written feedback within 60 calendar days for most submissions. A pre-RFD submission should not be confused with an RFD submission, which requires extensive information and results in a binding decision by the FDA on a sponsor’s device classification and pathway.

An Request for Designation (RFD) or “applicant’s letter of request” is a written submission to the FDA Office of Combination Products (OCP) to obtain a binding determination of the product’s classification and /or center assignment. RFDs generally request a determination of:

1. 1. The regulatory identity or classification of a product as a drug, device, biologic, or combination product, and/or
   2. The Agency Division of the FDA that will regulate the product if it’s a non-combination product, or which Agency Center will have primary jurisdiction for the premarket review and regulation if it’s a combination product.

The RFD should include a complete description of the product, modus operandi, the intended indications for use, and how the product will be marketed. For combination products, the submission should also include information on the relative contribution of each component.