With the tsunami of activities connected with the initial implementation of all the GDUFA requirements, another change made by FDA went largely under the radar. FDA released the draft guidance, “Pre-Launch Activities Importation Requests (PLAIR)”. (CDER July 2013) which describes how an NDA/ANDA applicant may import finished dosage forms into the United States prior to product approval. Interest has picked up recently by virtue of some potential conflict between this particular regulatory work-around and the Hatch-Waxman Act. (See FDA Law Blog and the analysis by Cheng and Avery) However, due to the “stealthy” premier of this guidance, it may be worth a review, especially for companies shipping from outside of the U.S..
The PLAIR guidance is a more formal approach to something FDA has done informally for some time. (Remember, INDUSTRY has to follow the rules; FDA? sometimes not so much.) The FD&C Act specifies that an unapproved drug cannot move in interstate commerce or be imported. (21 USC 355a) As a practical matter, FDA has created various mechanisms to allow unapproved drugs in various forms to enter the US prior to approval. (See, e.g., 21 CFR§ 314.410(a)(2)) Informal requests for importation of product prior to product approval have been being negotiated on a case-by-case basis for some time, exactly how long is hard to say. The PLAIR Guidance provides some formality and structure to this process. It has a good deal of potential utility for NDA/ANDA applicants whose products are manufactured outside the United States.
The guidance addresses:
- When and how a PLAIR can be submitted
- What information should be in the PLAIR
- When and how to submit a PLAIR
- How FDA intends to process a PLAIR
The guidance expends a good deal of narrative creating a rationale justifying the use of the PLAIR. In brief, ( and oversimplified) the submission of a PLAIR by an applicant, and its acceptance by FDA will create the expectation an “automatic” detention of the material by FDA along with an understanding that the applicant is offering to “recondition” the material via the impending approval.
A full and careful review of the Guidance is critical for anyone interested in submitting a PLAIR. A few specifics to keep in mind are:
- PLAIRs are meant for finished dosage forms either in final packaged form or in need of minimal further processing. (e.g., packaging and/or labeling)
- Applicants submitting a PLAIR must be appropriately registered unless exempt.
- If the PLAIR is granted, the materials to be imported must go to a single site,the amount must be specified, the site must be cGMP compliant, and the material must be placed under quarantine until approval .
- The PLAIR must be submitted at least 30 days prior to the proposed arrival date of the material, but no more than 60 days prior to the user fee goal date. (or the expected approval date for ANDAs filed before October 1, 2014)
- FDA will review the cGMP status of the foreign manufacturing site after receipt of the PLAIR as part of the assessment
The guidance provides a description of the mechanics of the PLAIR review but does not spell out decision criteria or time frames.
William P. Stoltman J.D.
Senior Director of Quality Assurance and Compliance