On January 14, 2021, the United States Food and Drug Administration (FDA)  kicked off the year with a set of Webinars for the trade community. Specifically, the Center for Drug Evaluation and Research (CDER) held its first annual Small Business and Industry Assistance (SIBA) Compliance Conference.  The topics covered various areas dedicated to compliance including compounding in cleanrooms, drug importation requirements, drug supply chain security act implementation, and Risk Evaluation and Mitigation Strategies (REMS) compliance.

Cristina O. Dar, who leads an import compliance team within the Division of Global Drug Distribution and Policy’s Office of Drug Security, Integrity and Response, gave the presentation on Human Drug Imports. During the presentation, Ms. Dar provided an overview of the human drug Importation Requirements, clarified importation requirements for different drug types, and discussed routes of importation for human drug products.

In order to uphold its mission to protect the integrity of the global supply chain throughout the drug lifecycle to minimize consumer exposure to unsafe, ineffective, and poor quality drugs, ODISR regulates the importation of human drugs. When these drugs are introduced at a port of entry, agents inspect the shipment to verify that the products comply with the various requirements.

FDA’s inspection of the items upon entry is crucial to maintaining public health. FDA must ensure that any imported drug has met the FDA’s standards for quality, safety, and effectiveness. FDA provided the most recent consequential example where FDA, in conjunction with U.S. Customs and Border Protection (CBP), identified hand sanitizers containing methanol. Hand sanitizers are over the counter drugs (OTC), and methanol is a toxic substance. Not only did the vigilant officers flag the imports, but FDA also came up with subsequent processes to prevent a future occurrence.

FDA’s Regulatory Purview

FDA works to ensure that all drugs (articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; articles (other than food) intended to affect the structure or any function of the body of man or other animals; and articles intended for use as a component of a drug [201(g)(1)] ) are not misbranded or adulterated. FDA is mandated with this responsibility under Section 801(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 301(a), as well as Section 501 of the FD&C Act. Under section 801(a) of the Act, an article (drug) is subject to refusal if it appears from examination or otherwise that:

  1. It has been manufactured, processed, or packed under unsanitary conditions (adulterated),
  2. Forbidden or restricted for sale in the country in which it was produced/exported,
  3. Is adulterated, misbranded, or in violation of section 505 of the Act.

Drug Importation Requirements

There are various requirements for the importation of human drugs to be deemed admissible. When the importation reaches a port of entry, FDA will verify that the shipment complies with the following requirements:

  • Registration and listing
  • New Drug Application (NDA); Abbreviated New Drug Application (ANDA); Center for Drug Evaluation and Research (CDER) regulated Biologics License Applications (BLAs)
  • Investigational New Drug (IND)
  • Compliance with applicable labeling requirements
  • Ensure that products/manufacturers are not on an import alert

Additionally, foreign manufacturers must be registered with the FDA upon importation with a list of all of its commercial distributed drug products (Section 501(i)). Further, all drugs being imported must be compliant with the General Labeling Requirements found in 21 CFR 201.1-201.328:

  • Product labeling should bear all required information in English
  • Exception: Label in Spanish for distribution in the Commonwealth of Puerto Rico is authorized under 21 CFR 201.15(c)
  • A prescription Drug (503(b)(1)) is required to include the “Rx only” symbol on its label (503(b)(4))

Active Pharmaceutical Ingredients (APIs) are considered to be drugs and must also be declared to FDA ((21 CFR 207.1). In addition to complying with the applicable requirements of the finished drug products, APIs must meet specific labeling requirements as detailed in 21 CFR 201.122.

Affirmation of Compliance Codes (AofCs) Qualifiers are three-letter codes that can be provided at the time of import to demonstrate compliance and facilitate FDA review of Import requirements. The A of Cs are only mandatory in some instances and not required for all scenarios. Submitting the A of Cs is voluntary and can facilitate the process by expediting initial screening and review. Included below is a list of A of Cs (not all-inclusive):

Intended Use Codes (IUCs) allow for the FDA to know the purpose of imported shipments. The IUCs dictate which A of Cs are applicable. IUCs differ from product intended use in that product intended use is the use for the patient, whereas the import intended use is the intended importation route of the product.

Routes of Importation

Currently, FDA allows for the importation of a product that is unapproved or otherwise does not comply with FDA laws and regulations if it is coming into the US for further processing or incorporated into a product for export and ultimately exported out of the US (Import for Export (801(d)(3) of the FD&C Act). Prescription drugs, however, can only be re-imported into the U.S. by the original manufacturer in certain situations, such as a recall, overstock, or return scenarios.

Personal Importation Policy (PIP): covers importation of a product not for further sale or distribution into US commerce.

  • FDA typically does not object to the personal importation of unapproved drugs that meet the criteria listed in Regulatory Procedures Manual (RPM) Chapter 9, Subchapter 9-2: Coverage of Personal Importations.

Non-clinical Research and Development Products are not intended for use in humans and are exempt from registration and listing requirements. Importers must ensure that the quantity is reasonable for the research to be performed. Additionally, it is often beneficial to include a statement of intended use (separate from the IUC) when these products are imported into the US. These drugs (includes APIs) are intended for use in non-clinical R&D to generate data needed to submit an IND. FDA may consider not objecting to its import. To assist FDA in its admissibility review of a drug intended for non-human R&D; helpful to include an intended use statement with the import entry documentation that:

  1. Provides a description of the drug’s intended use, including the specific research to be conducted;
  2. Affirms that the quantity offered for import is reasonable for the intended research use; and
  3. Affirms the drug will not be commercially distributed.

Pre-Launch Activities Importation Requests (PLAIR) allows, in certain circumstances, product sponsors anticipating approval of a drug application (NDA, ANDA, BLA) to import unapproved finished drugs products (FDP) in order to prepare for market launch. The amount of drug product imported into the US must match the amount in the original PLAIR submission, otherwise, an amended PLAIR should be submitted to CDER for approval.

Ensure that you understand the requirements and regulations relevant to your product, as FDA has little mercy if you do not.  Assure you stay compliant and avoid the top rationale for FDA to detain your goods by hiring someone that is extremely knowledgeable with FDA’s laws and regulations and continually stays up to date with the constant changes. If you have questions on human drug importations or FDA-related matters, contact Diaz Trade Law today at info@diaztradelaw.com or 305-456-3830.