USER FEE WAIVERS MOST LIKELY WILL BE GRANTED TO "SMALL ENTITIES"

USER FEE WAIVERS MOST LIKELY WILL BE GRANTED TO "SMALL ENTITIES" with annual revenues of less than $ 10 mil., according to FDA's interim guidance on waivers and reductions in user fees. "Although there is no express threshold for defining a small entity," the guidance says, "FDA generally considers an entity with less than $ 10 mil. in annual gross revenues and no corporate parent or funding source with annual gross revenues of $ 100 mil. or more . . . as less likely to be able to continue to provide products that benefit the public health and to develop innovative technology because of user fees." However, FDA does not plan to grant waivers to all firms that meet "small entity" criteria, the interim guidance emphasizes. At a recent Drug Information Association meeting, FDA Deputy Commissioner for Management and Systems Mary Jo Veverka proclaimed that FDA will be "hard-nosed" in allowing as few waivers as possible, and that most waivers, if granted, will be for product and establishment fees rather than application fees. The interim waiver document was included in a packet of user fee guidances sent to companies with invoices for products and applications the week of July 19. The other guidances provide FDA's thinking on the submission of separate applications and definition of clinical data, and fee implications for applications that have been withdrawn or refused filing. The invoices billed 114 companies a total of $ 28 mil. in user fees in the first round. Orphan drug applications may be eligible for fee waivers even though the applications may be submitted by pharmaceutical companies that are considered to be mid-sized under the waiver guidance. The guidance states that "products such as orphan drugs that are innovative and provide public health benefits may be candidates for application fee waivers or reduction, even when these products are developed by medium-sized entities with annual gross revenues of less than $ 100 mil." FDA added, however, that it "will consider requests for fee waivers or reductions for such products, but does not expect to grant them often." FDA recommended that companies wishing to be considered for waivers should submit their requests 90 days prior to the filing of an application. All fees are payable upon submission of the application "without regard to any pending request for a fee waiver or reduction," the guidance states. Small businesses may qualify for an exception to the application fee if they have "fewer than 500 employees, including employees of affiliates, and [do not] have a prescription drug product introduced or delivered for introduction into interstate commerce." Those companies pay half of the $ 100,000 application fee, and payment is deferred until one year after the date of submission. Waivers and reductions also may be granted in situations where the user fee exceeds the cost of FDA's review. The agency has hired the accounting firm Arthur Anderson to develop standard cost estimates to assist in evaluating requests for waivers or reductions in this situation. "Until these costs have been developed, FDA will hold any fee waiver or reduction requests submitted . . . in abeyance and will refund any monies paid should a fee waiver or reduction subsequently be granted under this provision," the guidance notes. In two separate guidance documents, FDA outlines separate refuse-to-file policy for NDAs, PLAs and establishment licensing applications. The guidances state that sections of NDAs and PLAs containing inadequate supporting data for additional indications will not be accepted for filing with FDA, while sections for other indications containing complete data will be accepted. Among the omissions of data or analyses that would trigger a Center for Drug Evaluation and Research RTF decision is "clearly inadequate evaluation for safety and/or effectiveness of the population intended to use the drug, including pertinent subsets, such as gender, age and racial subsets." This deficiency is also listed in the RTF guidance for the Center for Biologics Evaluation and Research. CDER announced in May that it had established a committee to evaluate the center's RTF decisions. The committee consists of senior CDER officials, a senior official from CBER and FDA Chief Mediator and Ombudsman Amanda Pederson. CBER is expected to develop a similar review mechanism in which CDER will be represented. A separate user fee guidance covering "bundling" also was sent out the week of July 19. Developed jointly by CDER and CBER, the guidance outlines situations for "bundling" into a single application different drug products, dosage forms, routes of administration, pharmacy bulk packs, strengths, container sizes or indications. The guidance does not allow major modifications to increase the number of indications covered by a pending NDA without submitting an efficacy supplement and an additional user fee, CDER Deputy Director-designate Murray Lumpkin, MD, told the DIA meeting July 13.