Earlier this week, the US Food and Drug Administration (FDA) launched the Expedited Access Premarket Approval program (EAP), a new program aimed at getting innovative medical device products to needy patients more quickly by expediting the regulatory review of the products and their manufacturing processes.
But in addition to the guidance document detailing the program, FDA also issued a draft guidance document on which clinical data FDA will expect companies to have available prior to approval, and which data it will be willing to accept after the device has been introduced to the market.
The guidance, Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval, isn't just applicable to the EAP program, FDA explained. Instead, it's aimed at all devices subject to its premarket approval (PMA) process-a rigorous review pathway used for most high-risk (Class III) medical devices.
At its core, the guidance is meant to address one of the timeless issues in regulatory: How can regulators balance the need to ensure a device is safe and effective with the needs of patients to have timely access to new medical therapies?
The collection of data, FDA notes, is supposed to rely on a "least burdensome" principle laid out in Section 513(a)(3)(D)(ii) of the Federal Food, Drug and Cosmetic Act (FD&C Act), meaning only those data which are "necessary to establish device effectiveness." The term is further defined in a 2002 guidance document.
Such data must be sufficient for FDA to make a determination about the benefits and risks of the product, and data from at least one (and often more) clinical investigation is typically required.
But here, FDA says, is where things begin to get difficult. "There is never 100% certainty when determining reasonable assurance of safety and effectiveness of a device," it explains in the guidance. The time and cost it would take to obtain close to 100% certainty would be prohibitive, both to companies and to patients waiting for new therapies.
As with pharmaceutical products, FDA is increasingly looking to take some of the data it historically sought prior to approving a drug-for example, data indicating long-term safety effects-and instead making it a postmarket requirement (PMR). In such cases, a company is required to submit clinical data to FDA at agreed-upon times. Failure to submit the data can permit FDA to revoke approval for the device, though in practice the agency often grants extensions. (FD&C Act Section 513(a)(3)(C))
But if regulatory professionals within the medical device industry enjoy one thing, it's transparent and consistent expectations from FDA, and FDA's data collection guidance aims to provide just that.
Specifically, it clarifies when PMRs may be appropriate at the time of a device's approval.
Many types of devices may be eligible for PMRs, FDA's guidance explains, including:
- devices incorporating "mature technology," defined as one with well-understood benefits and risks, and with a long history of testing and clinical use
- devices incorporating measures capable of mitigating known risks
- devices labeled with warnings, contraindications, precautions to alert patients to potential, probable or unknown risks
- if a device has two separate use populations, and the device has only been sufficiently studied in higher-risk use populations (leaving the lower-risk use to be studied post-marketing)
- devices intended to be used over a long period of time, when the long-term risks of the device are not yet known
- devices with possible rare adverse events
If a device is capable of being approved based on bench data (e.g. non-clinical data) along, then PMRs will likely be required.
FDA provides specific examples of each situation in its guidance.
FDA also notes that the postmarketing studies may require the submission of a PMA supplement, such as if new adverse events are identified, or if the trials indicate the device is less effective than first known. In addition, data obtained may result in FDA revoking approval if the benefit-risk assessment of the device changes based on new data.
Comments on the guidance are due by 22 July 2014.
Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval (FR)