Certain facilities, sites, and other organizations involved in the production of human generic drugs face an impending deadline under the Generic Drug User Fee Amendments of 2012 (“GDUFA”). Among other things, these entities must electronically submit self-identifying information to the U.S. Food and Drug Administration (“FDA” or “the Agency”) by December 3, 2012. FDA has issued a notice in the Federal Register as well as a draft Guidance for Industry to help organizations determine whether they are subject to GDUFA’s self-identification requirement and, if so, what information they need to submit.

Background
In July 2012, GDUFA was enacted in an effort to support efficient, timely review and approval of safe and effective generic drugs. The law requires, for the first time, that generic drug sponsors pay user fees to the Agency to help offset the costs of evaluating an abbreviated drug application and conducting related facility inspections. Between the current fiscal year and the one ending in 2017, FDA will receive $299 million annually from industry in user fees, in addition to the budgeted allowance granted to FDA, for evaluating the safety of generic drugs. Ostensibly, the law will provide industry with more reliable timelines and predictable application review on the basis of the additional resources provided by the submission fees.

In addition to the performance based goals and efficiency improvements, FDA will endeavor to foster certain aspects of regulatory science of particular interest in the development of therapeutically equivalent therapies. These include continuing to develop current or new bioequivalence standards for orally inhaled products, topically applied dermatological products, and gastro-intestinal products; continuing to develop science-based recommendations for product development and the evaluation of generic drugs once they are commercially available; and defining additional, relevant initiatives with feedback from an industry working group.

GDUFA went into effect October 1, 2012, thereby enabling FDA to collect user fees for subsequent generic drug submissions. The additional resources are intended to help cut the average review time for generic drug application safety, to help reduce the current backlog of more than 2,500 pending applications for new generic drugs, and to help increase the number of inspections the Agency conducts of the related facilities. FDA is required to report on the efficiencies gained as compared against performance goals set under the program. According to FDA, GDUFA will not only expedite the public’s access to generic drugs while reducing costs to pharmaceutical manufacturers but also will make the global supply chain safer by requiring certain organizations involved in the production of generic drug products to self-identify on an annual basis. The Agency plans to use the self-identifying information to construct an accurate inventory of such facilities, set annual facility fee amounts, and target inspections, among other things. GDUFA also requires generic drug facilities and sites to self-identify and register with the Agency.

In early October 2012, FDA published a Notice of Requirement in the Federal Register regarding the self-identification component of the law. The notice served to inform generic drug facilities and certain sites and organizations identified in a generic drug submission that they are required to provide identification information to the Agency. The notice is intended to help groups determine whether they need to self-identify and what information is required, as well as to provide them with the means and format for submitting the required information.

Who Must Self-Identify?
The following types of facilities, sites, and organizations (“self-identifying entities”) must submit self-identifying information to FDA:

• Facilities that manufacture, or intend to manufacture, an active pharmaceutical ingredient contained in a human generic drug (“API”) or a finished dosage form of a human generic drug (“FDF”). Notably, GDUFA defines API and FDF manufacturers differently from how they have been defined historically, as per the Guidance Document published in August 2012. As described in that document, for example, generic drug manufacturers that mix an API when the substance is unstable or cannot be transported on its own are considered API manufacturers and not FDF manufacturers for self-identification and the payment of GDUFA fees only. GDUFA defines an API as a substance, or a mixture when the substance is unstable or cannot be transported on its own, intended to be used as a component of a drug; and to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the human body; or a substance intended for final crystallization, purification, or salt formation, or any combination of those activities, to become such a substance or mixture. Moreover, the Act defines an FDF as a drug product in the form in which it will be administered to a patient, such as a tablet, capsule, solution, or topical application; a drug product in a form in which reconstitution is necessary prior to administration to a patient, such as oral suspensions or lyophilized powders; or any combination of an active pharmaceutical ingredient with another component of a drug product for purposes of production of such a drug product.
• Sites and organizations that package an FDF into the primary container/closure system and label the primary container/closure system.
• Sites that, pursuant to a contract with a company that has submitted a generic drug submission that identifies the site, either (a) remove the drug from a primary container/closure system and subdivide the contents into a different primary container/closure system, or (b) perform testing of one or more attributes of an FDF or API to satisfy a cGMP testing requirement. Bioequivalence (BE) and bioavailability (BA) sites that are identified in a generic drug submission and conduct clinical BE/BA testing, bioanalytical testing of samples collected from clinical BE/BA testing, and/or in vitro BE testing.

What Type of Information Must Be Submitted?
The information required is identified in GDUFA Structured Product Labeling Industry Technical Specification Information document. In its notice, the Agency highlighted the need to submit the name and contact information for both the registrant owner and the facility, if they differ. This information includes the type of business operation, and, if applicable, the Data Universal Numbering System (DUNS) number(s) and the Facility Establishment Identifier (FEI). A DUNS number is a unique nine-digit sequence provided by Dun & Bradstreet, Inc., while an FEI is a unique identifier designated by FDA to assign, monitor, and track inspections of regulated firms. A facility or site that has previously registered with FDA under certain provision of the Federal Food, Drug, and Cosmetic Act can verify its DUNS number(s) and FEI(s) on FDA’s registration site.

Finally, self-identifying entities must indicate whether they manufacture drugs that are not generic drugs. The Draft Guidance notes that some of the foregoing information may take time to obtain, a fact that entities should take into account when preparing to meet the upcoming deadline.

What is the Process for Submission?
Self-identifying entities should submit the above-described information in an SPL file created by any of the following tools:

• The eSubmitter tool available on FDA’s website.
• The Xforms tool available on FDA’s website.
• A software tool developed internally by the generic manufacturing utilizing the SPL technical specifications.
• A commercially available application.

The completed SPL file should be transmitted to FDA through the Electronic Submissions Gateway.

What is the Penalty for Failing To Self-Identify?
If an entity that is subject to GDUFA’s self-identification requirements fails to meet the requirements, all FDF or API products and all FDFs containing APIs manufactured at the facility will be deemed misbranded. Shipment of misbranded products in interstate commerce or importation of them into the U.S. constitutes a violation of Federal law. Such a violation can result in prosecution of those responsible, injunctions, or seizures of the misbranded products. FDA reiterates such consequences for failing to self-identify as part of the draft Guidance Document, stating that misbranded products will be subject to seizure if shipped in interstate commerce or imported into the U.S. Moreover, the entity itself may be prosecuted and/or be subjected to injunctive relief.

It is thus advisable that self-identifying entities begin the information collection and submission process as soon as feasible, noting the initial year’s program deadline: for fiscal year 2013, identification information must be submitted by December 3, 2012. In subsequent fiscal years, identification information must be submitted, updated, or reconfirmed on or before June 1 each year.

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Colleen Heisey is a partner in the Washington, D.C. office of Hunton & Williams LLP (www.hunton.com) and a member of the firm’s Food and Drug Practice. She can be reached at cheisey@hunton.com.
Sharon M. Bradley is an associate in the firm’s Food and Drug Practice. She can be reached at sbradley@hunton.com.