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By Cheryl Bolen
Dec. 26 — Long considered one of the most opaque of federal regulatory agencies, incidents of foot-dragging by the Drug Enforcement Administration (DEA) are now legendary among U.S. drug companies.
“It's a real problem,” said Daniel Kracov, partner and head of the health-care practice at Arnold and Porter LLP in Washington. Long delays by the Justice Department agency mean patients don't have access to drugs and companies lose exclusivity periods and money because they can't market their drugs, he said.
Meanwhile, the latest years-long—and still ongoing—review by DEA is to determine whether a highly regulated diagnostic test can become more widely available in the U.S. The victims in this struggle with DEA regulators are thousands of desperate patients seeking to confirm whether they have Parkinson's disease or some other type of degenerative nerve disorder.
The only known diagnostic test for Parkinson's disease that doesn't involve an autopsy uses a radioactive, Schedule II prescription drug called DaTscan, which is in danger of becoming even more limited unless the DEA acts. Drugs designated Schedule II by the agency “have a high potential for abuse which may lead to severe psychological or physical dependence,” according to the DEA.
At issue is the increasing amount of time it takes between the initial scheduling recommendation from the Food and Drug Administration (FDA) and the final scheduling decision and rule from the DEA.
The Controlled Substances Act is clear on each agency's responsibilities. The FDA has authority over scientific and medical matters, while the DEA has authority in the area of diversion risk and risk of abuse.
Under the statute, if the FDA recommends that a drug not be designated a controlled substance, the language clearly states that the U.S. attorney general shall not control it. The law, however, doesn't set a time limit for DEA action.
In 2011, the FDA sent a recommendation that the DEA decontrol DaTscan. This is usually a deliberative document, but both agencies have acknowledged that this was the recommendation that the FDA made.
It is now four years since the FDA's scheduling recommendation and the DEA hasn't acted—despite repeated requests, letters and meetings.
In a recent Nov. 26 letter to the DEA from GE Healthcare, submitted for the public docket, the company stated that “[w]hen DaTscan is no longer a controlled product the current barriers to access will quickly dissipate.”
When contacted by Bloomberg BNA for comment, an official at the Department of Justice would say only that “the matter is under review.”
Terry Mahn, managing principal at Fish & Richardson P.C. in Washington, said that for the past 30 years, one of the ironclad tenets of the Hatch-Waxman Act is the right to five years of data exclusivity for FDA-approved new chemical entities.
“This valuable ‘property right' was, and is still is, considered essential to incentivize manufacturers to invest in the discovery and development of new drugs,” Mahn said in an e-mail. “Thus, it comes as a great disappointment to many to witness two important federal agencies seeming to work at cross-purposes when they should be working for the common good,” he said.
Jeff Francer, vice president and senior counsel at the Pharmaceutical Research and Manufacturers of America (PhRMA), agreed.
“PhRMA supports better, more efficient coordination between the DEA and FDA to avoid delays in patient access to new medicines,” Francer said. “In addition, we should examine the coordination within FDA to determine whether there can be a more efficient process within the agency for ensuring timely drug scheduling,” he said.
DaTscan, manufactured by GE Healthcare, is widely used in Europe and Japan and, to a far lesser extent in the U.S., to diagnose Parkinson's disease.
DaTscan is a radiopharmaceutical, which is a tracer that can be injected into a patient and later scanned with a special camera. In this case, a radioactive iodine atom is attached to a transporter molecule that can cross the blood-brain barrier and collect in the area of the brain that changes with Parkinson's disease.
Parkinson's disease is difficult to diagnose. Symptoms, such as tremors, are common to other conditions, but they are treated differently, so differentiating between Parkinson's disease and other parkinsonism syndromes is critical.
Since DaTscan's introduction into the U.S., it has faced numerous regulatory barriers. The DEA is involved because the drug is attached to a molecule called ioflupane, which is derived from cocaine. Because of this, the DEA considers DaTscan part of the cocaine family.
In the U.S., DaTscan is the only drug regulated as both a radioactive isotope and as a controlled substance. Only a fraction of the number of patients who might benefit from DaTscan can access it in the U.S., compared with Europe and Japan, where it isn't regulated as a controlled substance.
Regulatory concerns have intensified in recent months because hospitals have lost some federal funding for the test and are less inclined to administer it at an operating loss. Out of some 450 hospitals using DaTscan, about 80 hospitals are now restricting its use.
One solution is to make DaTscan available to thousands of free-standing imaging centers, which are reimbursed under a different set of Medicare payment rules. This has the added benefit of not only ensuring the test is still available, but making it more easily accessible at more locations.
But unlike hospitals, imaging centers often aren't registered with the DEA to handle scheduled drugs, which would bring them under a whole new regulatory regime for disposal, security, licensing, staffing and background checks. So registering isn't an option for most of these clinics.
More than that, supporters of the drug say, there is no reason for these imaging centers to jump through hoops. DEA control is only necessary when a drug has the potential for abuse or diversion, and DaTscan has neither. It would take about 6,000 vials of the drug just to produce a noticeable effect in a person. according to the Parkinson's Action Network.
In the U.S., the volume of the drug is about 15,000 vials per year. The vials typically are calibrated and leave the factory with a name and specific destination, because of the shelf life of the radioactive isotope. Any vials not delivered would be noticed immediately under the system.
Jennifer Sheridan Palute, director of policy at the Parkinson's Action Network, said that if the DEA doesn't act soon, GE Healthcare may have to reconsider its production of the radiopharmaceutical.
The Parkinson's Action Network (PAN) is a nonprofit educational and advocacy organization that conducts the public policy work of the Parkinson's community, Palute said.
In 2011, when DaTscan was first approved, PAN sent a letter to the DEA asking that the drug be descheduled. Palute said that in the last eight to nine months, there has been a significant increase in pressure on the DEA to at least provide more information about why it has been slow to act.
Palute said DaTscan has been available in Europe for more than a decade and has been used in more than 450,000 patients there with no evidence of abuse.
PAN sent another letter to the DEA administrator in March 2014, again requesting that the drug be descheduled. Palute said her organization didn't get an official response, but that she was part of a meeting with DEA officials last spring. “They did not provide many details about what their concerns or objections were,” she said.
However, it was clear from the meeting that patient access wasn't the DEA's care or concern, Palute said.
“And I think what's frustrating from an organization that represents people living with the disease, or people who are navigating a diagnosis and possibly joining our community, is just the DEA not providing any information about why they're not making the decision,” she said.
GE Healthcare has been trying to remove the regulatory roadblocks that it has faced, Palute said. Still, there are always concerns that the company might have to discontinue the drug or that it will become too difficult for patients to access, she said.
“If I'm a company that spends a lot of time and money developing a new diagnostic tool, I'm looking for a return on investment,” Palute said. “And if the [return] is not there, I think at some point as a company you have to make the decision to either cut your losses, or continue operating at a loss,” she said.
The roadblocks faced by GE Healthcare also might have an impact on future innovation, Palute said.
“So if you have a failure like the DaTscan, what does that do to the future innovation of innovative diagnostic tools for Parkinson's or other unmet medical needs?” she said.
Another DEA delay involving a potential treatment for epilepsy prompted Rep. Joe Pitts (R-Pa.) to introduce legislation in March to require the DEA to act within 45 days of receiving a scheduling recommendation from the FDA.
The Improving Regulatory Transparency for New Medical Therapies Act (H.R. 4299), easily made it through the Energy and Commerce and Judiciary committees and drew co-sponsors from both ends of the political spectrum.
Companion legislation (S. 2862) was introduced in the Senate by Sen. Orrin Hatch (R-Utah), but both bills died when Congress adjourned for the year. Even so, they would only have applied to new drugs that had never been marketed in the U.S.
Still, Pitts said that he intends to reintroduce the bill early in the new year and that he expects it to pass early with broad, bipartisan support in the House and Senate.
Delays have been a consistent problem with the DEA, Pitts said. While drafting the legislation, Pitts said he learned that FDA must make the decisions related to scientific and medical matters, which are binding on the DEA. And in at least the last 15 years, the DEA hasn't made any scheduling decisions that are contrary to the FDA's recommendations, he noted.
“And still, patients are waiting months and months for DEA to make the same decision,” he said.
The legislation would remove the duplication of the review process, Pitts said. It would require the DEA to issue a final rule within 45 days of receiving the FDA's recommendation, so companies can begin marketing their drugs and patients get access to new therapies, he said.
“DEA would retain its authority to transfer a drug between schedules,” Pitts said.
When asked about the DEA's reaction to the legislation, staff from Pitt's office said the agency was not happy with the bill, likely because of “typical turf battle” concerns.
Pitts called it a “reasonable type of bill” and that constituents were frustrated and suffering. “And this is a solution that doesn't jeopardize anybody or anything—it just gives more predictability and transparency and speeds things up a little bit,” he said.
Agencies always want to protect their “turf,” or existing authorities, Pitts said. “We don't take away any turf, we just make them make a decision a little sooner,” he said.
Earlier this year, the Epilepsy Foundation issued a position paper urging support for the House and Senate bills and expressing serious concerns about the growing delays by the DEA in scheduling new drugs.
For patients in need of new treatment options, the six- to 12-month wait for the DEA to act seems inexplicable, the foundation said. “Without apparent cause or justification, the time period between initial drug approval by FDA and final scheduling by DEA has been increasing over the years,” it said.
From 1997-1999 and 2009-2013, the average time between FDA approval and the DEA's final scheduling increased from an average of 49.3 days to an average of 237.6 days, an almost fivefold increase, the Epilepsy Foundation said.
The DEA has no set timeline or transparency requirements to make scheduling determinations, it said. And during the time between FDA approval and a DEA scheduling decision, patients may not access new therapies.
Kracov, of Arnold and Porter, agreed that delays are a real problem for patients and drug companies.
“You can petition DEA to de-schedule things, or down-schedule things, but this has been a running issue for the last couple of years, that DEA is just like molasses in terms of scheduling-related issues,” Kracov said.
In addition to resource constraints, Kracov suggested the DEA doesn't seem to prioritize its regulatory and scheduling activities relative to the law enforcement side of the agency. “At least that's my perception,” he said.
“So you have these situations where companies wait around—at least one company has filed suit trying to get their exclusivity back, saying FDA shouldn't have started the exclusivity until the scheduling occurred,” Kracov said. “There's not a resolution of that yet,” he said.
In August, Eisai Inc. sued the FDA over the agency's triggering of new chemical entity exclusivity for two drugs before they could be marketed in the U.S.
Linda Bentley, who leads the FDA practice group in the Boston office of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo P.C., said she believes most diagnostics with controlled substances have only a small quantity in them and would be very hard to abuse.
Also, one would think the radioactive part of DaTscan would be of greater concern than the controlled substance part of it, she said.
Bentley said she is aware of a drug that includes a derivative of cannabis that has seen some success in clinical trials for treating types of childhood epilepsy and pain in cancer patients. “So, it's not an uncommon problem,” she said.
The DEA decides which schedule the drug belongs in, Bentley said. This usually happens after the FDA approves the drug, and it used to take about four months for the DEA to make a final decision, whereas now it's taking almost a year or in some cases longer, she said.
“It's frustrating for a company that's gone through the drug approval process [to wait for DEA], particularly if the drug has some sort of patent protection or it's a new molecular entity, and there are various types of exclusivities and patent protections that might apply to the drug,” she said.
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