The regulator explains how it determines when it’s appropriate to increase reliance on postmarket collection to reduce the extent of premarket collection to support premarket approval, in a document integral to the CDRH’s risk-based approach to regulation and the FDA’s broader fulfillment of the “least burdensome provision” of the FDCA. The guidance correlates with the Expedited Access Pathway program, for which the FDA provides guidance in a separate document.
In its guidance document clarifying its policy on balancing premarket and postmarket data collection during PMA reviews, the FDA writes that a “right balance” — specifically, offsetting the reduction of premarket data collection with an increased reliance on postmarket collection — will help speed up patient access to new devices. The guidance is aimed at helping sponsors determine when this is appropriate.
A “least burdensome provision” in the FDCA, as explained in the regulator’s 2002 Least Burdensome Guidance, requires that the role of postmarket information be taken into account when determining how much data should be gathered in the premarket setting to support premarket approval; and further, reliance on postmarket controls should be considered as a way to decrease the extent of premarket data collection for PMAs. In its 2012 Benefit-Risk Guidance, the FDA describes what it considers when making benefit-risk determinations during premarket reviews for certain devices, specifying that the degree of certainty of probable benefits and risks of a device is one of the considered factors. The regulator considers postmarket data part of this benefit-risk framework.
The “Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval” guidance explains that the FDA may allow the of use post-approval studies rather than premarket ones when there’s an acceptable degree of uncertainty related to risks and benefits in terms of the overall benefit-risk profile of the device at the time of premarket approval. Several examples of this are listed, including when mature technology is involved, in which case benefits and risks are well-characterized by a robust history of testing and clinical use, and migration when the documentation of design controls, risk analyses and prior performance studies on already-marketed devices can provide sufficient knowledge, among others.
The document also covers conditions of approval, which may include postmarket or labeling requirements. When post-approval data collection is appropriate, post-approval studies or surveillance may be required as an approval condition. The FDA may also impose labeling requirements as a PMA approval condition, as well as continuing periodic reporting on the safety, effectiveness and reliability of a device post-approval. The FDA also warns that certain postmarket actions may be appropriate as a result of approval conditions, including submissions of a PMA supplement, safety communications, panel meetings, administrative and enforcement actions, and panel meetings.
Separately, the FDA issued the Expedited Access for Device Guidance. As part of the Expedited Access Pathway program, which the document explains, and in a bid to make earlier patient access easier for devices demonstrating the potential to address unmet medical needs, the FDA may accept greater uncertainty related to the benefit-risk profile of a device at the time of approval — which it will counterbalance with postmarket data.
The EAP program borrows features from the CDRH’S Innovation Pathway, but is a separate and distinct initiative tailored to devices. One of the key features influenced by the Innovation Pathway is the Data Development Plan, which outlines premarket and postmarket data that will be collected in support of device approval.
The program is voluntary, must be requested by the device’s sponsor and requires approval from the FDA. To be eligible for the EAP program, a device must be intended for the treatment or diagnosis of a life-threatening or irreversibly debilitating disease. It must also satisfy at least one of the following criteria: there is no alternate treatment or means of diagnosis for the condition/disease; it signifies a technological breakthrough that would provide an advantage over existing marketed technologies; it offers an advantage over other existing marketed alternatives; or the device’s availability is in the best interests of patients.
When applying for EAP designation, the sponsor is required to include a description of the data collection plan, including the study plan and design. It should also include an explanation and justification for the proposed balance of premarket and postmarket data collection. Finally, it should include a timeline for the development and marketing of the device as well as the postmarket data collection. The FDA will respond to the sponsor within 30 days with its decision and, if necessary, the FDA may require the sponsor to submit additional information.