In Through the Out Door: FDA Issues Guidance on Its Importation of Prescription Drugs Final Rule

Channeling Led Zeppelin’s “In Through The Out Door,” in May 2022, the Food and Drug Administration issued a guidance for industry entitled, “Importation of Prescription Drugs Final Rule Questions and Answers (Small Entity Compliance Guide).”¹ The agency intends that the guidance should help companies comply with its Final Rule on importation of prescription drugs.² While we know that any guidance document is not legally binding, it represents FDA’s current thinking on the subject. FDA will accept comments at any time.

This Bulletin will highlight some of the key questions and answers raised in the guidance.

Who May Import Eligible Prescription Drugs?

• In an authorized Section 804 Importation Program (“SIP”), an Importer may import “eligible” (to be discussed below) prescription drugs.
• SIPs may be co-sponsored by, for example, a State, a pharmacist, or a wholesale distributor.
  • Authorization for a SIP will automatically terminate after two years from the date of importation of the SIP’s first shipment, unless a shorter period of time is specified in the SIP’s authorization.
  • SIPs may be modified, but only with FDA’s authorization.
• An Importer must be a licensed pharmacist or wholesale distributor who is the U.S. owner of an eligible prescription drug when bringing it into the U.S.
  • The Importer’s license must be active, in good standing with the licensor, and issued by a State that is a SIP Sponsor or SIP Co-Sponsor.

What Prescription Drugs Are “Eligible” for Importation?

• Section 804(b) is limited to importation of prescription drugs from Canada.
• To be eligible for importation, a drug must be approved by the Health Canada’s Health Products and Food Branch (“HPFB”) and must have HPFB-approved labeling when marketed in Canada.
• In addition, an eligible prescription drug must meet the conditions in an FDA-approved new drug application or abbreviated new drug application (except when not sold in Canada).
• The following (non-exhaustive) list of drug products are excluded from eligibility:
  • controlled substances;
  • biological products;
  • drugs that are injected intravenously, intrathecally, or intraocularly; and
  • drugs that are subject to a Risk Evaluation and Mitigation Strategy.³

Importation Process and Requirements

• How to Obtain Eligible Prescription Drugs
  • In an authorized SIP, a Foreign Seller, who is a licensed wholesaler by Health Canada and registered with FDA, will purchase an eligible prescription drug directly from the drug’s manufacturer and sell the drug directly to the Importer in the United States.⁴
  • Each drug’s supply chain must be limited to three entities (e., one manufacturer, one Foreign Seller, and one Importer).
  • If the Foreign Seller does not comply with applicable requirements, FDA cannot authorize the SIP or may discontinue it.
• Importation Requirements
  • After FDA has authorized a SIP Proposal, the Importer must submit a Pre-Import Request to FDA at least 30 calendar days before the scheduled arrival date or the date of entry for consumption of a shipment containing an eligible prescription drug covered by the SIP, whichever is earlier. See 21 C.F.R. § 251.5.
  • The Importer may not bring in eligible prescription drugs until the Importer receives formal notification from FDA that its Pre-Import Request has been granted.
  • Entry and arrival of a shipment containing an eligible prescription drug must only go to the U.S. Customs and Border Protection port of entry authorized by FDA.
  • The Importer (or its authorized customs broker) must electronically file a formal entry for consumption in the Automated Commercial Environment or another electronic data system authorized by CBP for each drug imported or offered for import.
  • Failure to comply can lead the government to refuse the product’s entry.
• Labeling Requirements
  • The drugs must be relabeled with the required U.S. labeling, including patient labeling, such as a Medication Guide, Instruction for Use documents, and patient package inserts.
  • The Importer’s National Drug Code for the eligible prescription drug must replace any other NDC otherwise appearing on the label of the FDA-approved drug. In addition, the labeling must include, among other things, the lot number assigned by the manufacturer, the name and place of business of the Importer, and the statement: “[This drug was/These drugs were] imported from Canada without the authorization of [Name of Applicant] under the [Name of SIP Sponsor] Section 804 Importation Program.” See 21 C.F.R. § 251.13.
• Testing Requirements
  • Either the manufacturer or the Importer must conduct testing to determine authenticity, check for degradation, and confirm compliance with established specifications and standards.
  • If the Importer will be testing the drugs upon arrival in the U.S., the Importer must select a statistically valid sample of that batch to send to a qualifying laboratory for Statutory Testing and submit a “Statutory Testing” plan as part of its Pre-Import Request. See 21 CFR § 251.17(d).⁵
  • If the manufacturer will be testing the drugs, then the manufacturer must provide protocols to support the required testing. See 21 CFR § 251.17(e).

Post-importation Requirements

• The SIP Sponsor is responsible for implementing a recall, if appropriate.
• Drugs imported under a SIP can be returned, but the SIP Sponsor must ensure that a product that is returned after distribution in the U.S. is not exported from the U.S.
• Each SIP Sponsor is required to provide FDA with data and information about its SIP, including the SIP’s cost savings to the public; SIP Sponsors and other SIP participants must also allow FDA to audit their books and records and inspect their facilities.
• Importers must submit adverse events, field alerts, and other reports to a drug’s manufacturer and FDA.
  • Importers must maintain records of information relating to adverse events, whether or not submitted to FDA, for 10 years. See 21 C.F.R. § 251.18

AGG Observations

• The Q&A Guidance provides useful insights to better understand FDA’s interpretation of the Final Rule concerning importation.
• Recordkeeping, data retention, and proper written policies after the drug product enters into the U.S. is as important as the steps taken to import the product in the first place.
• Failure to review FDA’s Final Rule and recent guidance can delay shipment of the prescription drug, which can have significant detrimental effects on a company; Stay informed (and we will update as appropriate).

[1] See https://www.fda.gov/media/158659/download.

[2] The Final Rule was issued in 2022 to implement 21 U.S.C. § 384(b), relating to the importation of certain drugs from Canada. See also 21 C.F.R. Parts 1 and 251; 85 Fed. Reg. 62094 (Oct. 1, 2020).

[3] See 21 C.F.R. § 251.2. For non-excluded drug products, FDA will determine whether the product can be imported safely in the context of a specific SIP Proposal on a product-by-product basis. A SIP Sponsor will need to explain in its SIP Proposal how it will address concerns arising from the manufacture, storage, and transport of each eligible prescription drug, including concerns related to contamination, sterility, and stability.

[4] The Foreign Seller cannot have an international pharmacy license that allows it to distribute drugs which are approved by countries other than Canada and that are not HPFB-approved for distribution in Canada. There are a number of supply chain requirements for Foreign Sellers (e.g., Foreign Sellers must separate the portion of drugs intended for sale to a United States Importer, and store such drugs separately from the drugs intended for sale in the Canadian market). See, e.g., 21 C.F.R. § 251.14.

[5] Statutory Testing means the testing of an eligible prescription drug as required by the Federal Food, Drug, and Cosmetic Act, including for authenticity, for degradation, and to ensure that the prescription drug is in compliance with established specifications and standards. See 21 C.F.R. § 251.2; see also 21 C.F.R. § 251.5(c)(4)(x).