FDA requires new drug applications for PET tracers made in cyclotrons

Medicare reimbursement for rubidium is on the horizon

Proponents of clinical PET suffered a serious blow late last monthafter the Food and Drug Administration announced that it wouldrequire PET facilities to submit new drug applications for theirformulations of cyclotron-based radioisotopes. The decision isexpected to create a major regulatory roadblock for facilitiesthat wish to provide clinical PET services.

In a sign of good news for the PET market, however, the HealthCare Financing Administration is said to be only weeks away fromissuing a long-awaited decision to provide Medicare and Medicaidreimbursement for PET studies using rubidium-82.

The agency's NDA announcement was published in the Feb. 27edition of the Federal Register. It concludes a regulatory processbegun in 1989, when the FDA said it wanted to review the statusof cyclotron-produced radioisotopes, which previously were regulatedunder practice of pharmacy rules.

In the Federal Register notice, the FDA stated that PET radiopharmaceuticalswill be regulated under the provisions of the Federal Food, Drugand Cosmetic Act, which stipulates that new drugs such as PETradiopharmaceuticals "must be the subjects of approved newdrug applications (NDAs) or abbreviated new drug applications(ANDAs) before marketing."

The FDA's decision is the PET industry's worst-case scenariofor regulation of PET radioisotopes, according to Dr. Steven Larson,president of the Institute for Clinical PET. Larson is also chiefof nuclear medicine at Memorial Sloan-Kettering Cancer Centerin New York and a professor of radiology at Cornell University.

"There is no question that the FDA's posture has pushedthis field back perhaps five years," Larson said. "Itis going to increase the concern of commercial PET manufacturersand also commercial radiopharmacies about the viability of thisas a business. It will dramatically increase the cost of a PETscan to patients."

The NDA process can drag on for years, as demonstrated by thecase of Downstate Clinical PET Center in Peoria, IL. The PET industrysponsored Downstate's submission of an NDA in 1990 for its formulationof 18-fluorodeoxyglucose (FDG-18) as a means of testing the FDA'spolicy, which was then a proposal. Five years later, Downstatereceived the agency's approval only for epilepsy applicationsfor PET. The FDA rejected Downstate's NDA for cardiac and brainapplications.

The Peoria experience is widely viewed by the PET industryas a failure, according to Larson.

"(The Peoria NDA) took five years and it is still an unsatisfactorysituation," Larson said. "We have only this one indicationto show for all that effort."

To add insult to injury, PET facilities submitting NDAs willprobably have to pay user fees on their applications, Larson said.User fees were established for the pharmaceutical industry in1992.

The ICP, along with several other professional associations,submitted a petition to the FDA in December urging the agencyto regulate PET radioisotopes under state practice of pharmacyand medicine regulations, which would have allowed individualPET sites to produce radioisotopes without requiring an NDA. Failingthat, the petition asked the FDA to set up PET drug review committeesto review the use of PET radiotracers for certain applications.The FDA apparently rejected the petition in ruling that NDAs orANDAs must be submitted.

For many facilities, the ANDA route might offer a quicker pathto clinical PET than an NDA. An FDA official, however, said thatANDAs are usually used for generic drug applications and wouldprobably not apply to PET radiopharmaceuticals.

Research PET sites will not be required to submit NDAs or investigationalnew drug (IND) applications as long as their research is not usedto guide or be a part of therapeutic, diagnostic or clinical managementplans, the notice states. These facilities should establish PETregulatory committees overseen by the FDA to monitor radiopharmaceuticaluse.

The FDA is sponsoring a public workshop on March 21 to provideguidance on the new rules. The workshop will be held from 8 a.m.to 4 p.m. in conference rooms G and H at the FDA's Parklawn Buildingat 5600 Fishers Lane, Rockville, MD. Those interested in attendingthe workshop should phone John Levchuk of the FDA at 301/594-0095.

One last hope for PET advocates could come from Republicanefforts to impose a moratorium on new federal regulations (seestory, page 1). Several moratorium bills are moving through theHouse of Representatives and Senate, although it is unclear whetherthese bills would apply to the new NDA rules.

On a positive note, HCFA appears to be close to approving Medicarereimbursement of PET applications using rubidium-82, which iscommonly used for cardiac applications. Rubidium-82 is not producedin a cyclotron and therefore is not covered by the FDA's new rules.

The PET industry has been expecting HCFA's decision on rubidiumsince last summer, when the Office of Health Technology Assessmentpassed on to HCFA an evaluation of rubidium in cardiac imaging(SCAN 9/14/94). The evaluation was the last milestone before federalreimbursement for rubidium studies could be issued.

Since then, the PET market has been anxiously awaiting HCFA'sgo-ahead. It's been some months in coming, but many sources closeto the agency believe that a decision could be forthcoming withinweeks.

A major beneficiary of federal reimbursement for rubidium willbe Bracco Diagnostics, which markets CardioGen-82, a generator-basedrubidium PET agent. Bracco acquired CardioGen-82 from Squibb Diagnostics,which Bracco bought last year. CardioGen received FDA approvalin 1990 (SCAN 1/31/90).