Common Rule Checklist

by Aarthi Iyer

Passports at the Ready: Exploring FDA’s Final Rule on Acceptance of Data from Clinical Investigations for Medical Devices

On February 21, the Food and Drug Administration (FDA) released the Final Rule on Human Subject Protection; Acceptance of Data From Clinical Investigations for Medical Devices, amending its regulations at 21 CFR Parts § 807, § 812, and § 814. The rationale behind this shift is to help provide greater assurance of the quality and integrity of clinical data obtained from clinical investigations and to promote the protection of human subjects.

In the spirit of exploring, understanding, and settling into a new regulatory landscape, the following discussion provides a high-level roadmap for navigating FDA’s journey to this Final Rule.

View from Above

At its core, the Final Rule calls on FDA applications that include clinical investigations conducted outside the United States to provide statements and information regarding how the investigations conform to Good Clinical Practice (GCP) standards. Rather than prescribing a particular GCP rule (e.g., International Conference on Harmonisation), FDA frames the view by identifying GCP as something similar to a city center where all roads meet. FDA defines GCP “as a standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical investigations in a way that provides assurance that the data and results are credible and accurate and that the rights, safety, and well-being of subjects are protected.” FDA’s GCP definition also includes review and approval by an independent ethics committee (IEC) before initiating an investigation, continuing IEC review of ongoing investigations, and obtaining and documenting the informed consent of subjects.

Spanning Six Distinct Terrains

Through this rule, FDA is amending regulations for a variety of submissions: premarket approval (PMA) applications, humanitarian device exemption (HDE) applications, investigational device exemption (IDE) applications, and premarket notification submissions. Additionally, the agency is modifying the IDE and premarket notification regulations to address the requirements for FDA acceptance of data from clinical investigations conducted inside the United States.

As with any new frontier, navigating and acclimatizing takes time. In an attempt to provide a seamless path between existing regulation and the Final Rule, FDA has stated that the effective date will be February 21, 2019—one year after the publication of this Final Rule in the Federal Register.

Traversing Multiple Borders

FDA notes that for a multicenter investigation with sites both inside and outside the United States, each site would need to comply with local regulations, which makes for a dizzying itinerary of regulatory coordination and compliance on an international level. For multinational investigations that include sites in the United States, the Final Rule stipulates that the determination of the institutional review boards (IRBs) overseeing the sites in the United States should be used.

In considering the subtle differences between domestic IRBs and foreign IECs, FDA recognizes that IECs may not be familiar with FDA’s terminology related to significant risk and non-significant risk device investigations. As such, under the IDE regulations, sponsors and applicants may make an initial determination, with rationale, for investigations conducted outside the United States.

The Sea of Data Privacy

The European Union’s General Data Protection Regulation (GDPR) is looming on the horizon and data privacy laws vary markedly across the globe. Perhaps because of this, several public comments on the rule stated that stricter privacy laws outside the United States may restrict the ability of sponsors and applicants to comply with the rule’s requirements around:

  • Assuring the availability of data and copies of patient records for FDA validation through onsite inspection, and
  • Names and addresses of investigators.

Most of these provisions remain unchanged in the Final Rule, with FDA navigating the wake of public commentary as follows:

  • Historically, when needed to validate data from clinical investigations conducted outside the United States, FDA has been able to inspect the records of these investigations. FDA obtains the consent of foreign governments before conducting foreign inspections. If the agency believes that access to records is necessary to verify certain data or validate the investigation, and such records are not available because of foreign law, the sponsor and FDA will need to agree upon an alternative means of validation.
  • The Final Rule does not require investigators’ personal addresses, but it does maintain that the names and addresses of all facilities that took part in the investigation are required, buoyed by the European Commission’s recognition of ISO 14155:2011, which includes providing names and addresses of investigators to regulatory authorities.

A Safe Harbor

While the Final Rule does have some murky waters, FDA provides a safe harbor in recognizing there may be situations where full conformity with GCP may be difficult or not feasible. Commenters noted that in at least one country IECs will not review post-market on-label studies because the committees’ scope is limited to investigational studies. In such scenarios, if the sponsor or applicant cannot meet GCP for the investigation, they may provide an explanation of the departure from GCP or request a waiver. § 812.28(c) of the Final Rule allows sponsors and applicants to request a waiver of any applicable requirements, with adequate justification, prior to: a) initiation of an investigation or b) submitting an application or submission supported by clinical data from investigations conducted outside the United States.

The Road Ahead

The Final Rule provides a solid foundation to build from, but there is always room for additional development. In response to public comment that FDA develop a guidance document similar to the one available for investigational new drug applications (INDs), the agency perceptively agreed and intends to issue guidance that explains the requirements of the rule in plain language and how sponsors and applicants can comply with the requirements.

In the interim, if updating your policies, SOPs, agreements, and records sounds as complex as a round of Settlers of Catan, Kinetiq is here to help you use your resources strategically in preparing your medical device regulatory submissions.


James Riddle

Executive Insight

James Riddle, MCSE, CIP, CPIA, CRQM, VP of Client Services

Technological innovations have traditionally outpaced regulation. Encouraging to see FDA keeping pace in this area. If your organization needs help navigating these waters, our team at Kinetiq can help.

Tags: , , , , , , , , , , ,