Over the past few weeks I’ve had several conversations with manufacturers and consultants alike regarding the export of an Unapproved Investigational Device for use in a Clinical investigation to be conducted entirely outside the United States.
One of the first comments I get asked: does the FDA have jurisdiction? While the answer is easy, it is surprising to some: yes, the FDA does have jurisdiction over the export of the investigational device. But if the clinical trial is done entirely outside the United States, the FDA has no say in the trial itself.
Of course, if you want to make sure the data will be accepted by the FDA, you may want to obtain an IDE exemption before you start the foreign trial. But, maybe not.
US law (Food, Drug and Cosmetics Act) provides two ways to export an unapproved investigational device. In practice you will choose between these two ways based on the country where you will hold the clinical trail
FDA approved Devices
If your product is FDA approved 510(k) or PMA, the US will allow export without restrictions, and below does not apply, whether or not the device is used for Investigational purposes.
Below therefore applies only to devices that have not received prior approval.
Tier-1 Countries
The law lays out which countries are considered Tier-1: Australia, Canada, Israel, Japan, New Zealand, Switzerland and South Africa as well as any country that is part of the European Union or the European Economic Area.
Beware: In case the UK choses for a very hard Brexit, they may lose their Tier-1 status (in which case Secretary of Health and Human Services will probably decide to designate the UK a Tier-1 country).
Exporting an unapproved investigational device to a Tier 1 country is fairly easy. While no prior approval by the FDA is required., the device must comply with some basic rules:
• The device needs to be manufactured by a cGMP approved facility
• The device cannot be adulterated other than by lack of marketing approval
• The device cannot present an imminent hazard to the public
• And must be labeled and promoted in accordance with the requirements and conditions for use in the country to which the device will be exported.
Furthermore, the exported products need to be:
• In compliance with the specifications of the foreign purchaser
• Not in conflict with the laws of the foreign country to which the device will be exported
• Labeled on the outside of the shipping package that it is intended for export.
• And must not be offered for sale in the US.
While no prior approval is required, the manufacturer must notify te FDA of the export. Furthermore, the manufacturer must prove that the rules were complied with when the FDA shows up for an audit.
This means for instance that the manufacturer must be able to show that the product shipped where the products ordered by the purchaser, or that the product is not in conflict with the laws of the importing country.
This last requirement could be met in two ways;
A letter from the appropriate agency in the foreign country stating that the product does not conflict with the country’s laws
or,
A notarized certification by a responsible US company official that the product does not conflict with the laws of the country to which it will be exported. Anyone signing this statement needs to acknowledge in their statement that the certification is subject to Title 18 section 1001 – Statements or entries generally
Non Tier-1 Countries
Non Tier-1 countries are more difficult to export to. The exporter will have to prove that the device being shipped is not a threat to public health or to safety before it will be allowed to be exported.
This requirement gets omitted only if:
• The device has been approved for marketing in one of the tier-1 countries
• The company has received IDE approval from the FDA
Or
• The manufacturer was informed by the Institutional Review Board that the device is a non-significant risk device and the device will be used in clinical trials in the importing country for the same intended use.
Furthermore, the exported products need to be:
• In compliance with the specifications of the foreign purchaser
• Not in conflict with the laws of the foreign country to which the device will be exported
• Labeled on the outside of the shipping package that it is intended for export.
• And must not be offered for sale in the US.
The above only gives a cursory overview of the requirement a manufacturer wanting to export an unapproved investigational device must meet. Manufacturers considering such an export should inform themselves about all the requirements stated in the law and regulations.
Besides the export, companies should also consider the import of their device in the target country. Another issue which can benefit from thorough review.
Above serves informational purposes only. DO NOT rely on above guidance to make determinations regarding the export requirements regarding your investigational devices. Instead, do refer to the legal texts governing such exports (21 USC 381 , 21 USC 392) and look at:
Exporting Unapproved Devices or Guidance for industry Exports under the FDA export Reform and Enhancement Act of 1996 for additional guidance.