Regulatory Focus™ > News Articles > New Guidance Clarifies Process for Bringing Drugs into US Prior to Approval to Expedite Market Acces

New Guidance Clarifies Process for Bringing Drugs into US Prior to Approval to Expedite Market Access

Posted 24 July 2013 | By Alexander Gaffney, RAC 

A new draft guidance document released by the US Food and Drug Administration (FDA) on 24 July 2013 concerns so-called Pre-Launch Activities Importation Requests (PLAIRs), requests to FDA to allow the import of unapproved finished dosage form drugs based on an anticipated approval of a pending drug application.

Background

The launch of a pharmaceutical product is often a massive deal for drug companies, particularly for smaller companies that may have invested enormous amounts of capital into getting a product approved. Even for larger companies, the approval of a potential blockbuster can bring needed relief to both the company's bottom line and its share prices.

In order to capitalize on the opportunity to quickly bring a product to market after approval (and to take advantage of more of the product's period of market exclusivity), some companies will begin manufacturing a product even before it has obtained approval from FDA. This may be done if, for example, an FDA advisory committee overwhelmingly votes to recommend approval for a product, making its eventual approval highly likely.

Difficulties may arise, however, when a company seeks to import those still-unapproved products-usually manufactured abroad-into the US to await final labeling and packaging. Under the Federal Food, Drug and Cosmetic Act (FD&C Act) (Section 505(a)), the import and distribution of unapproved products into interstate commerce is prohibited, and Section 801(b) of the Act allows FDA to refuse admission to products that would violate Section 505(a).

A PLAIR request, however, is submitted to FDA asking for a variance to allow that product to be imported to prepare for a market launch. If a PLAIR is granted, FDA will detain the drug for up to six months while the approval decision is pending. In FDA terminology, a "detention" can mean that the drug products must be confined to a particular facility, may not be altered further and may not enter interstate commerce, but all relevant details are at the discretion and direction of FDA.

New Guidance

In the past, FDA notes that it has considered PLAIR requests on a case-by-case basis, and has offered some basic informal guidance to industry at some of its Small Business Assistance conferences.

Now, though, it is seeking to "create a more formal program, and this guidance outlines what information should be submitted to FDA in a PLAIR, when and how a PLAIR can be submitted, and the circumstances under which [FDA] intends to grant a PLAIR," the agency writes in the draft guidance.

A drug must meet certain basic, minimum standards in order to be considered by FDA for a PLAIR. For example, it must:

  • only require "minimal" further processing such as labeling or final packaging or already be in final packaged form
  • be manufactured by a firm registered with FDA and not under any import alert
  • be the same product that is currently undergoing an application review process at FDA
  • be submitted to FDA no more than 60 days before the user fee goal date for the completed review of the application for a new drug application (NDA) or biologics licensing application (BLA), and 60 days for any abbreviated NDA filed after 1 October 2014.
  • be submitted no later than 30 days before the anticipated user fee decision date to allow time to process the request
  • meet current good manufacturing practice (CGMP) standards per 21 CFR 210 and 211, as determined by FDA's Office of Drug Security, Integrity and Recalls (ODSIR), a division of the Center for Drug Evaluation and Research (CDER)

Detention Procedures

As explained earlier, FDA's definition of "Detention" permits the drug product to be stored at a manufacturer's facility so long as FDA approves of the applicant's site and it meets CGMP requirements.

"For an unapproved finished dosage form drug product that calls for minimal further processing, that the bulk 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," FDA explained.

Thereafter, the drug will need to remain at that facility or be transferred to a "single site consisting of a warehouse or a distribution facility" controlled by the applicant either directly or by contract. Once there, the drug must remain under quarantine and under the legal control of US Customs and Border Protection (CBP). Nearly identical procedures are in place for already-finished drug products not requiring further processing.

If the drug product is approved within six months, FDA will release it for sale. If, however, it is not approved, the products will be refused admission into interstate commerce, and will need to be either exported or destroyed within 90 days.

FDA's PLAIR Guidance

Federal Register


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