By: Liz Tompkins, International Logistics Supervisor, Myoderm
Clinical trial managers should be aware that recent organizational changes within the FDA’s Office of Regulatory Affairs are causing drug importation delays. As of May 15, 2017, FDA field offices that process imports are now part of the Office of Regulatory Affairs and are divided into five new Import Divisions1. The FDA’s Office of Regulatory Affairs is the lead office for all FDA field activities as well as providing FDA leadership on imports, inspections, and enforcement policy. Simultaneously, the FDA is establishing a more stringent policy on documentation needed at time of import. Given these changes, there are likely to be delays and increased inspections of all unapproved drugs entering the United States.
The most common cause of delays in FDA processing and release is missing or inaccurate information. Importers should work closely with their brokers to navigate these new policies and processes to reduce the chances of an import delay. Below is an overview of the documentation required for each of the three main categories of unapproved drugs.
Investigational New Drug (IND)
This category includes drugs that, once cleared, typically enter a Phase 1 clinical trial. The FDA reviews the application for safety to ensure that research subjects will not be subjected to unreasonable risk. Importing under an IND requires an End Use Letter—preferably on the sponsor company’s letterhead—that contains the following information:
- IND number and exact drug name (including code names) as listed on the IND filing with FDA
- Full name and address of sponsor company, as listed on the IND filing with FDA
- If the drug being imported is a comparator, ancillary or pharmaceutical necessity to the drug listed on the IND filing
- Study or protocol number
Research & Development (non-human use only)
This category is specific to drugs that are intended for investigational use in laboratory research animals or in vitro testing. Importing under this category requires an End Use Letter and should contain the following:
- Intended use, e.g. laboratory testing, compatibility testing, stability testing
- Confirmation that it will not be used in humans or distributed commercially
- Confirmation that all unused material will be disposed of in a way that does not expose humans to risk, either directly or indirectly
- Full name and address of sponsor company or US testing site
IFE (Import for Export)
This type of import covers products that, in their current state, do not comply with FDA regulations and therefore require extra reporting and accountability to the FDA. It is recommended that caution is taken before importing anything under an IFE and that a regulatory expert be consulted for more information on this type of import.
In most cases, when the above information is submitted electronically and on-time, the FDA will issue a release. However, if the information is not complete and clear at the time of importation, the FDA will place the unapproved drug on hold and forward to compliance. This step can add weeks to the review and release process and may result in refusal of entry. Alternatively, the FDA may request additional documentation, such as a Certificate of Analysis (CoA).
If a CoA is unavailable, the FDA will accept other documents. CoA’s or equivalent documentation should provide the product’s formulation, ingredients, components, or results of analysis determining the presence of a substance and the amount (i.e. assay), as appropriate to the type of article. (section 801(d)(3)(A)(i)(III)).
CoA’s for drug products could include:
- Documents to assure the identity of the substance and its components in the chemical and drug industries
- A batch certificate
- Documents, including a CoA, that establishes a drug ingredient is certified to meet USP requirements
- Documents that provide the level, potency, identity, strength, quality, and purity of the drug component, and whether a prohibited material has been used in the imported article
As you strive to keep your clinical trial on schedule, consider these FDA organizational changes and adjust timelines accordingly. If possible, work closely with your broker to make adjustments that will ensure the FDA is receiving the information they need to issue import releases as quickly as possible.