Recent Warning Letters from FDA about Medical Devices: Investigational Device Exemptions and Lack of Marketing Authorization the Focus

Over the past several months, the Food and Drug Administration (FDA) has issued a number of Warning Letters related to Investigational Device Exemption (IDE) requirements and misbranding. An IDE allows an investigational device to be used in clinical studies to collect safety and effectiveness data to be included in premarket approval (PMA) or premarket notification (510(k)) submissions to the FDA.


Unless exempt, a clinical study of an investigational device must have an IDE in effect upon initiation. In addition, the study must have an investigational plan approved by an institutional review board (IRB). Among other things, the sponsor is also required to obtain patient informed consent; ensure that labeling states that the device is for investigational use only; maintain the requisite records and reports for the study; and monitor the study.

FDA Warning Letters

On September 5, 2017, FDA issued a Warning Letter to Dynavision International, LLC based on an inspection of the Dynavision D2 product, an attention task performance recorder. FDA determined the Dynavision D2 device to be misbranded because the firm failed to submit a new premarket notification prior to introducing the device into interstate commerce with a major change to its intended use. In a July 31, 2017 FDA Warning Letter, FDA stated that the EYE-SYNC device is similarly misbranded because it was introduced into interstate commerce with major changes to its intended use without a new premarket notification. FDA also found these devices to be adulterated because they did not have PMAs or IDE applications on file.

On June 21, 2017, FDA issued a Warning Letter to a sponsor-investigator based on the company’s failure to obtain an IDE (and related offenses) for clinical studies of two products that are combinations of two previously cleared devices. FDA stated that the combination devices had not been approved or cleared by the FDA. FDA noted that, although the two devices are made up of two previously cleared devices, Socket Graft and OsseoConduct, the combination of the two devices constitutes a significant change or modification that requires the sponsors to submit IDE applications to the FDA and obtain approval prior to allowing subjects to participate in the investigations.

FDA issued an April 6, 2017 Warning Letter to Entellus Medical, Inc. resulting from an inspection of the sponsor activities for a clinical study, conducted under an Investigational Device Exemption. FDA found that the sponsor failed to obtain FDA and IRB approval prior to implementing a change to the investigational plan and failed to secure compliance by investigators with the IRB approved protocol and related documents. More specifically, the IDE application was approved for the treatment of the maxillary sinuses in children 2 to 12 years old. Investigators, however, treated frontal and sphenoid sinuses in children under 12 years of age without first obtaining approval. FDA noted particularly that a request to treat frontal and sphenoid sinuses in children had been specifically denied by FDA prior to the treatment of these subjects and that FDA had expressed safety concerns with this treatment on several occasions.

AGG Observations

  • Sponsors and investigators should be aware of the federal regulatory requirements for an IDE, review past FDA statements and obtain requisite FDA and/or IRB approvals prior to initiating a clinical investigation.
  • Recent FDA activity indicates that an IDE may be required when two previously cleared or approved devices are combined.
  • While a few Warning Letters over the past several months does not make a trend, it does seem that Investigational Device Exemptions and a lack of marketing authorization is on FDA’s radar. It is important to be attuned to marketing claims and review marketing issues, including the legal, regulatory and quality control components.