FDA issues final guidance for importing drugs prior to anticipated approval

Background

Under the Federal Food, Drug, and Cosmetic Act (FDCA), importing a “new drug” is generally prohibited unless the drug is the subject of an applicable approved application. However, historically, FDA has, on a case by case basis, allowed sponsors of certain drugs for which approval is anticipated to request permission to offer for import such unapproved drugs using a “PLAIR” – a Pre-Launch Activities Importation Request – pursuant to which the drugs are detained under Customs bond and released for distribution only after being “reconditioned” once FDA approves the relevant application.

Last week’s final guidance describes when and how a PLAIR can be submitted, and explains the circumstances under which FDA intends to grant a PLAIR.

Which drug products are PLAIR-eligible?

The PLAIR program covers finished dosage form drug products that are the subject of a pending NDA, ANDA, or CDER-regulated BLA, that either a) call for minimal further processing, such as final packaging and/or labeling; or b) are in final packaged form. The final guidance lists what should be included in a PLAIR applicable, such as the National Drug Code (NDC) number, a letter from FDA officially documenting the user fee goal date, the precise quantities to be imported, and the facility identification number (such as the DUNS) and telephone number of any facility where the finished dosage form drug product in final packaged form will be stored pending approval.

In addition, an authorized representative of the applicant must certify the following:

• The applicant’s acknowledgment that the product is an unapproved new drug;
• That the PLAIR represents the applicant’s request to “recondition” the product by obtaining product approval within 6 months;
• For an unapproved finished dosage form drug product that calls for minimal further processing, that the unapproved finished dosage form drug product will be delivered to a facility identified in the finished dosage form drug product’s pending application to permit further processing, and that following completion of those activities, the product will remain subject to the terms and conditions of the U.S. Customs and Border Protection (CBP) entry bond that covers the specific shipment.
• For an unapproved finished dosage form drug product in final packaged form that does not call for further processing, that the drug product should be delivered to a single facility used for warehousing, and that the product will remain subject to the terms and conditions of the CBP entry bond that covers the specific shipment;
• That the facility used for warehousing complies with any applicable current good manufacturing practices (CGMP) or if applicable, other federal or state requirements.
• That the applicant understands that the unapproved finished dosage form drug product must be exported or destroyed within 90 days of the date of any notice of refusal, if refused admission.

Which drugs are not PLAIR eligible?

The following drugs would not qualify for the PLAIR program, as described in the guidance:

• FDA does not intend to consider PLAIR applications for drugs for which a supplement must be approved or submitted before the drug can enter commerce. The program is limited to unapproved drugs offered for import pending approval of original applications for approval, not drugs for which require approval of a Prior Approval Supplement or submission of a Changes Being Effected supplement. However, the guidance states that such products could still be offered for import and detained, and such products may be released by FDA if they are ultimately reconditioned by obtaining the necessary approval.

• Although not expressly addressed by the guidance, FDA has also historically taken the position that a PLAIR will not be approved for importing physician prescription drug samples. However, to the extent that such samples would ultimately be covered by an approved application, it would appear that FDA has the legal authority to extend the PLAIR program to such drug samples. Even without approval of a PLAIR, as for drugs awaiting approval of a prior approval supplement, a sponsor may offer such products for import and have them detained until such time as the relevant approval is obtained.

• Historically, FDA has stated that the use of a Foreign Trade Zone (FTZ) is an alternative to a PLAIR, and, therefore, FDA would not consider a PLAIR for a product shipped to an FTZ.

• Active pharmaceutical ingredients or excipients are not covered by the program, which is limited to finished dosage form drug products.

• CBER does not participate in the PLAIR program for BLAs under CBER jurisdiction. Therefore, biological products that must obtain approval of a BLA under CBER jurisdiction as a condition for marketing may not be imported under the PLAIR program, but may still attempt to obtain CBER/ORA authorization, on a case by case basis, for pre-launch importation either under enforcement discretion or subject to refusal and reconditioning upon approval.

Timelines

The PLAIR should be submitted at least 30 days prior to the proposed entry date of the shipment to allow time to process the submission. For PLAIR-eligible ANDAs, NDAs, and CDER-regulated BLAs subject to standard review, the PLAIR should be submitted no more than 60 days before the user fee goal date.

In addition, new in the final guidance, FDA advises sponsors subject to priority review to submit their PLAIR earlier:

• For PLAIR-eligible NDAs and CDER-regulated BLAs subject to 6-month (priority) review, the PLAIR should be submitted up to 120 days before the user fee goal date.
• For PLAIR-eligible ANDAs subject to priority review, the PLAIR should be submitted up to 80 days before the user fee goal date.

The final guidance also adds to the draft version clarification that if a firm makes changes to the initial PLAIR, it should explain all changes made, and identify the document as an “amendment” to differentiate it from the initial PLAIR request.

FDA will review the reconditioning request, and then once the drug arrives at the port of entry, FDA will issue a “Notice of FDA Action-Detained” for any product associated with a granted PLAIR. If FDA approves the underlying NDA, ANDA, or BLA, FDA will issue a “Release after Detention.” However, FDA requests notification of any deviation, such as labeling changes, for the product detained under PLAIR as compared with the product ultimately approved. If FDA refuses to approve the application, or 6 months otherwise elapse without FDA approval, the agency may determine that the product is subject to refusal and may issue a “Notice of FDA Action-Refusal of Admission.”

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If you have any questions on importing drugs or biologics, or on preparing your product for launch, you may contact any of the authors of this alert or the Hogan Lovells attorney with whom you generally work.

Authored by David Horowitz and Meredith Manning