The significant growth of clinical supply import laws to the US has resulted in more rigorous interpretation and enforcement of import laws and regulations to ensure supply chain quality. Clinipace’s international team of quality assurance and regulatory professionals help companies navigate this complex process every day. Here are some of the key challenges alongside my recommended solutions.
- Stricter Interpretation of US Import Laws. To ensure that only authorized drug imports get through customs, the FDA created an import database that cross references drug approvals and investigational new drugs (INDs). Unlike previous practice, now you must have an IND in effectbefore importing Active Pharmaceutical Ingredients (API)/drug products into the US. While not a new law, it can now be strictly enforced. An IND is considered in effect only when the 30-day IND review period has passed without notice of any open clinical hold items. But waiting to ship the API/drug product until the IND is in effect can result in significant costs and delays. Be sure to plan in advance and work with a knowledgeable customs broker and an experienced quality and regulatory group.
- Obtaining an IND Without Clinical Supplies. The FDA recently began requiring a Certificate of Analysis be included in the IND, but you can’t get an IND without testing the API/drug product. You can import a limited quantity of API/drug product to complete release testing and put some samples on stability. If the API manufacturing requires a larger batch, the contract manufacturing organization (CMO) might be able to ship only the quantity needed for testing and store the rest until the IND is in effect. If the drug product equipment requires a large quantity, potential solutions include: adding a statement about minimum batch size to the importation paperwork, finding a US-based CMO to create a smaller quantity, finding a foreign CMO to ship what you need and store the excess, or manufacturing the API and drug product in the US.
- Preventing Costly Delays. If a small amount of API is shipped to the US for manufacturing the test batch, consider the cost of the test batch and API and delays in getting supplies to the trial sites, which can be perhaps two months. Failure to understand the new requirements can result in an import refusal. The entire shipment must be exported back to its country of origin, requiring new documentation and adding perhaps another month to your schedule. Advanced planning and communications are essential.
- Get Your Docs in a Row. Be sure to adequately complete the required documents. For the End Use Letter, include the applicable Code of Federal Regulation references and the name and number of your IND. Identify and provide contact information for the API manufacturer, consignee, importer, and customs broker. You may choose to include a Prototype Exemption letter to eliminate paying an import tariff. The letter states that the material is for investigational purposes and will not be offered for sale.
- Other Recommendations. Identify a customs broker early, as setting up the initial paperwork can take a few weeks. If you decide to expand to global trial sites, each region/country has its own regulations and challenges, so I advise engaging a truly global team of experienced quality and regulatory professionals to ensure that applicable FDA and importation requirements are met and product quality is maintained throughout the supply chain.
If you’d like to learn more, I’ll be presenting at the March 27 webcast on Outsourcing Clinical Supplies Manufacturing: Navigating US Import Laws. Reserve your spot today.