PHILADELPHIA -- The FDA has set ambitious goals forspeeding new drug applications (NDAs) through the pipeline --paid for by the new user fees. A day-long discussion with drugand biotechnology company representatives here last weekfocused largely on how companies can navigate the newprocess.
Currently, median time from submission to approval is 12months, but applications may drag out for four years. The newgoals, to be achieved by 1997, are 12 months maximum forNDAs and six months for priority NDAs.
User fees are buying new manpower, and FDA is encouragingcompanies to submit higher-quality applications that won't clogthe regulatory pipeline. At submission, "applications should becomplete and ready for review," said Murray Lumpkin, deputydirector for review management at the Center for DrugEvaluation and Research (CDER).
Companies should refrain from amending applications underreview with new indications or clinical data other than thoserequired by safety updates or requested by the division. "Wedon't want someone to bring in five new indications and saythis is a supplement," said Lumpkin.
Forty-five days after submission of priority applications and 60days after other applications, FDA will send an "action letter"indicating approval, the need for more data, or refusal to file,meaning that the application lacks sufficient information forreview.
Many NDAs flounder because they omit key manufacturingdata. One frequent problem is inability to correlate lots fromclinical studies with those made in the facility to be licensed.
Other applications languish under the weight of unhelpfulinformation. Lumpkin urged that companies omit individualcase reports describing clinical experience to justify changes inadverse-event labeling, data used to add restrictions thatwould improve safe use of a drug, and bioequivalency studiesusing clinical end points that form the sole basis of approval.
The site inspection is pivotal; nothing hurts more thandeficiencies in good manufacturing process. A survey ofexamples in 12 biotechnology companies included, indescending frequency, standard operating procedure violations,equipment problems, deficiencies in controls on raw materials,processing, records, miscellaneous, laboratory controls andenvironmental monitoring, said Michael Beatrice, associatedirector for regulatory and public affairs for the Center forBiologics Evaluation and Research (CBER).
Successful applications usually involve a coordinated effortamong the different disciplines within a company, includingR&D, quality and regulatory affairs, said Joseph Phillips,assistant regional director for the mid-Atlantic region of FDA.
User fees fall into three categories: application fees, annualproduct fees and annual establishment fees. A company thatmarkets drugs subject to user fees must pay a product fee foreach drug and an establishment fee for itself. For fiscal year1993, product fees are $6,000, establishment fees are $60,000,and application fees are $100,000, plus $50,000 forsupplements. Each fee will increase annually, more thandoubling by 1997.
User fee waivers are available to needy companies. Companieswith fewer than 500 employees and that have no drugs on themarket, for example, must pay only half the normal applicationfee. Companies that want waivers should file 90 days beforerequired fees are due.
Companies also may recoup funds that exceed FDA's costs.
More than 60 percent of biotechnology NDAs will be priorityapplications, said Beatrice. Companies that may have priorityapplications should make that known at the time of submission,and they should begin working with the appropriate division ofCBER -- vaccines or therapeutics, for example -- much earlier.
"At 45 days after submission, we make a determination ofpriority based in large part on what the company says aboutthe application," although classification may be changed untilapproval, said Lumpkin.
The next FDA Industry Exchange Meeting on Implementation ofthe FDA User Fee Program will be held Oct. 6 in Burlingame,Calif.
-- David C. Holzman Washington Editor
(c) 1997 American Health Consultants. All rights reserved.