WASHINGTON - Under pressure from hospital and hospice groups, the FDA last Thursday said it is permitting an unapproved form of morphine sulfate used to treat pain in dying patients to stay on the market, reversing a decision the agency made last month.
Regulators on March 30 sent letters to nine manufacturers and distributors of unapproved morphine sulfate, hydromorphone and oxycodone in various strengths and forms warning the companies to stop making and distributing the narcotics.
However, after speaking with patient advocates Thursday, the FDA determined that it was medically necessary for morphine sulfate elixirs at the 20 mg/mL dose to remain available until an equivalent drug is approved, said Doug Throckmorton, deputy director of the FDA's Center for Drug Evaluation and Research.
He emphasized that Thursday's action only affects the 20 mg/mL morphine sulfate oral concentrate solution. The firms that received the warning letters for the other narcotics, including morphine in other forms and strengths, must still comply within 60 days of the FDA's earlier warning to cease production, Throckmorton told reporters during a media briefing. While there are approved forms of morphine sulfate on the market, there is a certain patient population for whom there are no other routes of administration that are as useful and effective as the high-concentrate 20 mg/mL oral solution, he said.
Roxane Laboratories currently is the only manufacturer who has an FDA approval to sell morphine immediate-release products in the U.S. However, Throckmorton noted, there are no approved formulations at the 20 mg/mL immediate-release oral solution concentrate.
Dying patients unable to swallow, but who need to control severe pain, need to be able to hold the elixir in their mouths, Throckmorton explained. "The other approved products are less concentrated and so it would be a larger amount of liquid in the mouth that would put them at risk for aspiration into the lungs" and other potential adverse effects, he explained. "So it is a population that is at the end of their life and needing this kind of pain control that doesn't really have other options at present."
Throckmorton said firms would be allowed to make and sell the 20 mg/mL morphine sulfate elixir in the interim "while we work on a longer-term solution."
The FDA, he said, would not take any action on the unapproved 20 mg/mL morphine sulfate elixirs until 180 days after the approval of a similar product or until other therapies are available to sufficiently meet the need of controlling pain in terminally ill patients unable to receive narcotics through other routes of administration.
Regulators have been aware for decades that thousands of drug products are sold on the U.S. market with unapproved labeling. About 2 percent of all U.S. prescriptions are for drugs with unapproved labeling, according to the FDA.
Michael Levy, director of the FDA's Division of New Drugs and Labeling Compliance, noted that there are a "variety of historical reasons" why unapproved products remain on the U.S. market.
Most notably, he said, is that several companies have been operating under an assumption that their older products are protected under changes in the 1938 and 1962 laws, called "grandfather clauses," which allowed exemptions of certain new drug effectiveness requirements.
However, Levy contended, "we think it is extremely unlikely that there is any product on the market today that is actually subject to the grandfather clause."
The FDA in June 2006 announced that it planned to crack down on manufacturers that make and distribute products with unapproved labeling. Regulators issued a final guidance document, called "Marketed Unapproved Drugs - Compliance Policy Guide," which outlined the FDA's approach for bringing unapproved drugs into compliance with the approval process.
Over the past nearly three years, the agency has been using a risk-based enforcement program to concentrate its resources on those products that pose the highest threat to public health but without imposing undue burdens on consumers or unnecessarily disrupting the market, Throckmorton explained. He said the agency has been moving through a list of unapproved products as quickly and as efficiently as possible to get the most dangerous drugs off the market.
The agency's first target under its 2006 initiative was carbinoxamine-containing products marketed to treat cough and cold symptoms.
Since then, the FDA has gone after makers of unapproved narcotics, quinine sulfate, trimethobenzamide, colchicine, ergotamine and other products.
In its most recent action, which came Friday afternoon, the FDA said it had obtained a permanent injunction barring East Windsor, N.J.-based Advent Pharmaceuticals Inc. and its subsidiary Neilgen Pharmaceuticals Inc., which also goes under the name Unigen Pharmaceuticals Inc., from manufacturing and distributing unapproved prescription cough and cold medicines and other drugs. Under a consent decree, the firms have been ordered to destroy their existing drug supply. The decree also prohibits the companies from commercially manufacturing and distributing any new drugs without the FDA's approval, regulators said.
DOD Teams with VA for Electronic Records
President Barack Obama last week unveiled plans to create a joint electronic health network that will contain administrative and medical information from the day a person joins the military until the day the soldier, airman, sailor or marine dies. The joint virtual lifetime record, a project of the Department of Defense (DOD) and the Department of Veterans Affairs (VA), is intended to provide seamless delivery of health information of military personnel and veterans.
Obama has proposed the system as a model for the entire nation. He noted that currently there is no comprehensive system in place that allows for a streamlined transition of health records between the DOD and the VA.
When a member of the armed forces separates from the military, the person will "no longer have to walk paperwork" from a DOD duty station to a local VA health center, the president said. "Their electronic records will transition along with them and remain with them forever," Obama declared.
Obama pledged that the "strictest and most rigorous standards of privacy and security" would be in place to ensure that military personnel and veterans can be confident that their medical records would only be shared at their direction.