20 May FDA Gets Creative to Encourage Innovative and Lifesaving Technology
In recent months, the United States Food and Drug Administration has introduced a number of mechanisms to encourage the development of novel, innovative, and life-saving medical technologies. This is, in part, due to the perception that many innovative products are being made available overseas long before they are accessible to patients in the United States. Many times companies are deterred from going through what is perceived to be a more stringent and costly process of meeting FDA regulations to gain market access in the US. As a result they conduct clinical trials and gain device approval in other countries. Early Feasibility Studies, The Expedited Access Pathway, and Acceptance of valid clinical data from foreign clinical studies are just three examples of the FDA’s creative methodology for encouraging U.S. Innovation.
Early Feasibility Study Investigational Device Exemptions
Owen Faris, the acting Clinical Trials Director at the FDA, stated that “Innovative medical products begin with clinical trials.” (1) This thought aligns with the FDA’s 2013 Guidance titled “Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies.” This guidance put into place a program to allow medical devices in the early stages of development to be approved for investigation under the IDE program in order to provide the “earliest and broadest patient access to beneficial medical devices.” (2) The FDA hopes that by allowing early feasibility investigations, product innovation will not move overseas.
What is an Early Feasibility Study (EFS)?
Early feasibility studies are intended to provide proof of principle and initial clinical safety of a device in the early stages of development, and are characterized by a small number of subjects. (3) These studies help manufacturers to gain insights into whether the device is user friendly, whether it achieves it intended use, and the safety of the device and the procedure. This helps to refine the device design, intended use, or device related procedure. (2)
These studies are necessary when there are few nonclinical testing methods and in-human studies are needed to gather information to finalize the device design. Since this clinical trial pathway by design is meant for devices that may still be in development, an EFS IDE may be approved with less device testing than would be expected with a traditional IDE application. (2)
The FDA established the process for Early Feasibility Studies for IDEs in the 2013 Guidance. They introduced new methods to allow for device and clinical protocol modifications characteristic of Early Feasibility Studies while remaining in compliance with Investigation Device Exemption regulations. The FDA intends to allow for:
- “Permitting a broader array of modifications to the device and the clinical protocol under 5-day notification without prior FDA approval during an early feasibility study as compared to other types of studies.”
- “For anticipated changes that would require prior FDA approval, allowing a sponsor to seek contingent approval beforehand, which would permit changes contingent upon acceptable nonclinical test results without requiring additional FDA action.”
- “For early feasibility study IDE supplements and amendments, utilizing a new interactive review process that encourages communication with FDA during the 30-day review cycle.”(3)
Allowing novel medical devices to be investigated at an early developmental stage with less nonclinical data has the potential to save manufacturers money and resources. This program could help to encourage innovation and allow patient access to breakthrough technologies in less time.
Expedited Access Pathway Program
The FDA’s Expedited Access Pathway (EAP) program was finalized in April 2015, by the guidance “Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions.” The intention of this program is to reduce the time and cost associated with market authorization. As the name of the program suggests, this will hopefully allow patients quicker access to life-saving devices. (4)
Eligibility and Scope of the EAP
Not all devices qualify for the EAP program. The FDA identifies two required criteria for acceptance into this program:
- Device must show the potential to address unmet medical needs for life-threatening or debilitating diseases or conditions
- Device must either:
1) Require a premarket approval application (PMA) or
2) Be eligible for a de novo request. (4) (5)
The program is voluntary and offers device sponsors an FDA case manager, priority review, a more interactive review with the FDA, and FDA senior management involvement. Also, approval through this program requires less data or evidence of safety and effectiveness than traditional FDA submissions (for PMA eligible devices only). This does not come without a price though, because the sponsor will be required to conduct more postmarket surveillance activities as a condition of the PMA approval. Essentially, the program redistributes some of the required clinical evidence from the premarket phase to the postmarket phase. (6)
It is important to note that de novo requests are not eligible for all of the perks offered by the EAP program. The FDA provides a table showing what aspects of the EAP program are available to PMAs versus de novos (4):
|EAP component||PMA||De Novo|
|Earlier and more interactive review with FDA staff, pending available resources||Yes||Yes|
|Data Development Plan||Yes||Yes|
|Conditions of Approval||Yes||No|
How to Participate
In order to participate in the program, the sponsor should contact the FDA early on in the device development process to ensure that all the required evidence of safety and effectiveness is gathered for the de novo request or Premarket Application. (6)
To formally request participation in the EAP program, the sponsor should submit a pre-submission to the FDA’s document control center, specifically identifying the submission as a request for EAP designation. Included in this pre-sub should be a draft Data Development Plan.
The Data Development Plan should include:
- Summary of the data collection plan
- Outline of planned and already completed testing, both clinical and non-clinical
- Summary of the nonclinical and clinical completed studies
- Proposed labeling
- “Explanation and justification for the proposed balance of premarket and postmarket data collection, if applicable.”
- “A timeline for the development and marketing of the device, and for the postmarket data collection, if applicable.” (7)
The program became effective April 15, 2015. Once a track record has been established, the industry will be able to determine if the EAP actually does provide quicker access to the US Market. (5)
Acceptance of Clinical Data from Foreign Studies
Acceptance of clinical data from foreign studies to support a premarket application is not a new concept, however the FDA’s policy for accepting data from Outside the United States (OUS) was somewhat of a mystery. Also, the regulations only addressed OUS data in support of PMAs, not 510(k)s, IDEs, and other regulatory submission. On April 22, 2015 the FDA issued a draft guidance discussing their standards for clinical data from studies conduction outside the United States. The FDA explains in this guidance that they recognize that clinical research is occurring on a global scale, and that sponsors may use such clinical trials to support market authorization (for all device submissions) within the United States. When the guidance is finalized, the FDA will be ensuring that new and innovative technologies can still be made accessible to US patients, even if the clinical studies are conducted elsewhere. (8)
Meeting FDA’s Standard for Valid Scientific Evidence
In order for the FDA to accept OUS data for a device submission, the data must constitute “valid scientific evidence.” (8) Listed below are the key considerations sponsors should address when choosing to use OUS data in support of a U.S. Device Submission.
- Clinical Conditions: if the standard of care or abilities of the physicians in a country are lower or significantly different from the United States, the data may not apply to US clinical practices. Make sure that the investigation is/was conducted in conformance with Good Clinical Practice (GCP) standards and with the Declaration of Helsinki.
- Study Populations: Differences in race, ethnicity, age, gender, and sex of the foreign population being studied can affect the how accurately the trial reflects safety and effectiveness for the intended United States population. Different populations also tend to have different risk factors or pre-existing health conditions. If there is a significant difference between the study population and the intended patient population, the sponsor should be prepared to explain why these differences will not impact the device’s safety and effectiveness.(8)
- Regulatory Requirements: Different countries have different sets of regulations for clinical trials, and often the expected endpoint for an OUS trial will not match the required US endpoints. For example, an OUS clinical trial may be conducted with the aim of determining performance, however in the United States the expected endpoint is proof of safety and effectiveness (by weighing risk and benefit). Leveraging OUS data intended to prove performance would not be sufficient to support a premarket application in the US. Sponsors should ensure that their endpoint will serve to support device approval with the FDA by keeping US Regulations in mind. (8)
The elements listed above should align with or exceed the FDA’s expectations in order for data to be considered applicable to a US device submission. The FDA suggests several times in the Guidance that seeking input from the FDA through a pre-submission is good way to ensure that data gathered in an OUS trial will be found acceptable to support market approval. (9)
What this means for your Company
The United States lays claim to the largest medical device market on the globe. The United States is home to both the largest consumption and production of medical devices. The market is set to grow at an annual compounded growth rate (CAGR) of 6.1% from 2013-2018 (10). This means that gaining earlier access to the US market can be an extremely beneficial for device manufacturers. The FDA is striving to make access to the US market easier, without compromising their standards for safety and effectiveness (2). Early feasibility studies for IDEs, The Expanded Access Pathway, and use of OUS data for US approval are all avenues that companies can take to expedite market authorization. However, these programs are still new, and it has yet to be determined if they actually will reduce time and cost for sponsors. These pathways should be carefully weighed against traditional methods of market authorization in both to US and Worldwide to determine if they are best option for your company.
Boston Biomedical Associates can assist with devising a strategic regulatory plan for medical device development and approval. We are actively engaged with the FDA and supporting clients with their EFS and EAP applications. Please contact us by email at firstname.lastname@example.org or fill out our contact form.