FDA Releases Guidance on Facility Registrations, Payments Under GDUFA

Two new draft guidance documents published by the US Food and Drug Administration (FDA) instruct owners of manufacturing facilities that produce generic drug products on how to comply with the terms of the newly enacted Generic Drug User Fee Amendments (GDUFA) of 2012.

GDUFA, enacted as part of the Food and Drug Administration Safety and Innovation Act (FDASIA), includes among its many provisions one requiring all generic drug facility sites and companies with products on the US market to register annually with FDA. The policy has been perceived by legislators as a potential answer for a long-troubling question: How can FDA regulate what it doesn't know exists?

"Self-identification is a central component of an effort to promote global supply chain transparency," explains FDA in one of the draft guidance documents. "The information provided through self-identification will enable quick, accurate, and reliable surveillance of generic drugs and facilitate inspections and compliance."

Draft Guidance: Who and What to Identify

FDA's first draft guidance document, Self-Identification of Generic Drug Facilities, Sites and Organizations, provides information regarding who needs to self-identify as a producer of generic products and what information they must provide to FDA.

All facilities, foreign or domestic, will be required to register with FDA if they have products involved in the US global supply chain. This includes manufacturers of active pharmaceutical ingredients whose products may wind up in US products by way of another manufacturer, facilities that package or repackage generic drugs and sites that provide testing on APIs.

Sites that generate bioequivalence (BE) or bioavailability (BA) testing to support product approval will not be required to register with FDA, though they will still be required to self-identify.

Bringing Parity Back to Inspections

Under GDUFA, such facilities will be required to pay FDA user fees, which will in turn go toward giving FDA the resources necessary to properly inspect the facilities on a more regular basis. Under existing law, FDA had the resources to inspect domestic firms on a regular basis, but not foreign firms, leading some manufacturers to cry foul as their foreign competitors enjoyed relatively lax oversight and fewer regulatory burdens.

The inequity of the situation has not been lost on top FDA officials.

"We need additional resources to provide the level of oversight that we believe is adequate," said FDA Commissioner Margaret Hamburg in remarks before the House Energy and Commerce Committee in February 2012. "Parity between domestic and foreign manufacturers would go a long way in securing the domestic drug supply and stemming the flow of manufacturers out of the country."

What to Disclose

The draft guidance document also explains the penalties for manufacturers who fail to self-identify, which officials said will be much easier to track once a new electronic self-identification system is operational. Two systems will eventually be in place: one for those required to register under the Federal Food, Drug and Cosmetic Act and another for those regulated under the Public Health Service Act.

Required information will include the registrant's name, company DUNS number, contact information, name of the facility, DUNS number for the facility, physical address, establishment registration number (FEI), type of business operations and contact information.

Draft Guidance: Q&A on What to Pay

FDA's second draft guidance, Generic Drug user Fee Amendments of 2012: Questions and Answers, pertains to the fees that will be payable to the agency. The fees, unlike those set for other drug products and medical devices, will only be calculated once all facilities and sites register with FDA.

Once established, fees will be levied on all abbreviated new drug applications (ANDAs), prior approval supplements, drug master files (DMFs), facilities on an annual basis and any pending applications held up in FDA's backlog.

In prior comments, Russel Wesdyk, director of FDA's Office of Pharmaceutical Science (OPS), said the fees are necessary to cover the agency's growing resource constraints. Funding for the generics program has remained flat since 2001, said Wesdyk, while ANDA submissions have more than tripled and DMF submissions have doubled. The result: a massive backlog of more than 2,700 applications that has nearly doubled since 2006.