The FDA issues final guidance on drug importation ahead of expected approval

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Last week, the U.S. Food and Drug Administration (FDA) released the final Pre-Launch Activities Importation Requests (PLAIR) policy, which outlines its policy regarding requests for importation of unapproved finished dosage form drugs by an applicant, manufacturing the product for US launch based on the anticipated approval of a pending NDA/BLA/ANDA. The final guidance largely mirrors the corresponding July 2013 draft guidance, except that it requires sponsors of drugs or biologics subject to priority review to submit their PLAIR filing with the FDA well in advance of the target royalty date Submit. As we discuss below, the PLAIR program outlined in the guidance can help pharmaceutical and biotechnology companies seeking FDA approval prepare their product for launch, including entering into distribution agreements, ahead of expected regulatory approval.

background

Under the Federal Food, Drug, and Cosmetic Act (FDCA), importation of a “new drug” is generally prohibited unless the drug is the subject of an appropriate approved application. However, in the past, the FDA has permitted, on a case-by-case basis, sponsors of certain awaiting approval drugs to apply for permission to offer such unapproved drugs for import by submitting a “PLAIR” — an Import Application for pre-approval activities Market launch – use where the drugs are held under bond and only released for distribution after “preparation” once the FDA has approved the relevant application.

Last week’s final guidance describes when and how to submit a PLAIR and explains the circumstances under which the FDA intends to issue a PLAIR.

Which medicines are suitable for PLAIR?

The PLAIR program includes finished dosage form medicinal products that are the subject of a pending NDA, ANDA or CDER regulated BLA that either a) require minimal further processing, such as: B. final packaging and/or labelling; or b) in end-packaged form. The final guidance lists what should be included in an applicable PLAIR (such as a DUNS) and the phone number of each facility where the finished drug form drug product will be stored in the final packaged form pending approval.

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

  • The applicant’s admission that the product is an unapproved new drug;
  • That the PLAIR represents the applicant’s request to “recondition” the product by obtaining a product approval within 6 months;
  • For an unauthorized finished medicinal product this requires minimal further processingthat the unapproved finished drug product will be shipped to a facility identified in the pending application for authorization to further process the finished drug product and that the product will remain subject to U.S. Customs and Border Protection requirements upon completion of such activities (CBP) Entry Guarantee covering the specific shipment.
  • For an unauthorized finished medicinal product in a ready-packaged form that does not require any further processingthat the drug product should be shipped to a single facility used for storage and that the product remains subject to the terms of the CBP entry guarantee that covers the specific shipment;
  • That the facility used for storage meets all applicable current Good Manufacturing Practices (CGMP) or other federal or state requirements as appropriate.
  • That the applicant understands that if the authorization is denied, the unapproved drug in finished dosage form must be exported or destroyed within 90 days of the date of a denial notice.

Which medications are not suitable for PLAIR?

The following drugs would not qualify for the PLAIR program as outlined in the guidelines:

  • The FDA does not intend to review PLAIR applications for drugs that require a supplement to be approved or submitted before the drug can be commercialized. The program is limited to unapproved drugs that are offered for import pending approval of the original regulatory submissions, not drugs that require a prior approval supplement or submission of a variation supplement. However, the guidance states that such products could still be offered for import and withheld, and such products could be cleared by the FDA if eventually remanufactured by obtaining the necessary approval.

  • Although not specifically addressed in the guidance, the FDA has also historically taken a position that a PLAIR should not be approved for the import of prescription drug specimens from physicians. However, to the extent that such samples would ultimately be covered by an approved application, the FDA appears to have legal authority to extend the PLAIR program to such drug samples. Even without the approval of a PLAIR, as with drugs awaiting approval from a prior regulatory supplement, a sponsor may offer such products for import and have them held pending approval.

  • In the past, the FDA has stated that using a Foreign Trade Zone (FTZ) is an alternative to a PLAIR, and therefore the 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 dosage form drugs.

  • CBER does not participate in the PLAIR program for BLAs under CBER’s jurisdiction. Therefore, organic products that require approval from a BLA under CBER jurisdiction as a condition of marketing may not be imported under the PLAIR program, but may still seek a CBER/ORA approval for pre-approval on a case-by-case basis -Introduction to obtain import either at the discretion of enforcement or subject to rejection and reprocessing after approval.

timelines

The PLAIR should be submitted at least 30 days prior to the proposed shipment arrival date to allow time to process the submission. For PLAIR-eligible ANDAs, NDAs, and CDER-regulated BLAs subject of a standard testthe PLAIR should be transmitted no more than 60 days prior to the Utilization Fee Target Date.

In addition, new to the final guidance, the FDA is advising sponsors subject of the priority examination to submit your PLAIR earlier:

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

The final guidance also adds clarification to the draft version that if a firm makes changes to the original PLAIR request, they should explain any changes made and mark the document as “change” to distinguish it from the original PLAIR request .

The FDA will review the reconditioning application, and once the drug arrives at the port of entry, the FDA issues a “Notification of FDA Action – Detained” for each product associated with a granted PLAIR. If the FDA approves the underlying NDA, ANDA, or BLA, the FDA will issue a “release after imprisonment.“However, the FDA requires notification of any discrepancy, such as B. Labeling changes, for the product held under PLAIR compared to the product ultimately approved. If the FDA denies approving the application, or otherwise 6 months elapse without FDA approval, the agency may determine that the product is denied and a “Notice of FDA Action – Denial of Approval.”

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