Vol. 7 No. 223
The FDA will seek advice on whether proposed surveillance programs for Pain Therapeutics’ Remoxy XRT abuse-deterrent painkiller and Alpharma’s Embeda are able to determine whether the products are abused after approval.
Two agency advisory committees — Anesthetic and Life Support Drugs and Drug Safety and Risk Management — are slated to discuss two issues: the available methods for assessing whether novel painkiller formulations are being abused and whether evaluation plans for Remoxy (oxycodone) and Embeda (morphine sulfate/naltrexone HCl) will accomplish the goal, according to briefing documents for the joint meeting scheduled to begin Thursday.
Pain Therapeutics’ Remoxy XRT is being reviewed Thursday, and the review of Alpharma’s Embeda is scheduled for Friday (DID, Nov. 12). King Pharmaceuticals has marketing rights to Remoxy XRT and has assumed development costs.
The proposed risk evaluation and mitigation strategy for Remoxy calls for monitoring abuse and diversion rates through review of scientific literature, media reports and the internet. The use of NAVIPPRO, a surveillance system that monitors misuse of prescription drugs, is included in the program. The system was developed with support from the National Institute on Drug Abuse.
The plan includes physician education on appropriate uses of the drug, including “dear healthcare provider” letters, company-sponsored education, independent continuing medical and pharmacy education, training for sales representatives and education efforts through disease and product websites.
The company proposes to use websites to educate teenagers about the risks of painkiller abuse.
Alpharma also plans to use NAVIPPRO, the company says. Endo Pharmaceuticals and Alpharma are founding members of the service.
All medical professionals who are certified by their state boards to prescribe painkillers and are registered with the Drug Enforcement Administration will be given a medication risk management kit.
The company also will fund education programs for physicians on the appropriate prescribing of Embeda, its misuse and abuse.
Physicians will receive a copy of a standard patient opioid agreement, a screening tool and instructions for performing a urine drug test. “As an example of its utility, an opioid agreement enables a commitment between the prescriber and the patient to treat pain appropriately while handling opioid medicines with care,” Alpharma says in briefing documents for the meeting. “Documentation of a patient screening and results from a urine drug test provide prescribers with guidance on whether patients may need additional provisions when prescribed opioids.”
Each patient prescribed Embeda will be monitored, Alpharma says. Each opioid agreement limits patients to filling their prescriptions at one pharmacy. Physicians are responsible for monitoring patient compliance with the agreement by using clinical judgment, the company says.
Other Committee Questions
The FDA will ask committee members to weigh in on the potential safety implications of “legitimate patients” being exposed to low levels of naltrexone, one of Embeda’s ingredients.
Naltrexone is an opioid antagonist. It passes through the body with no clinical effects when the pill is taken as directed. But when it is crushed, both ingredients are released and naltrexone reduces the euphoric effect of morphine, Alpharma says. The antagonist has been used as a component of other painkillers.
Additional questions include how effective the antagonist is in creating a product that is less easily abused and “how should the ease of separation of the opioid and the antagonist be considered in the assessment of these products, and whether a minimum standard can be set for how readily releasable the antagonist should be upon physical manipulation,” the FDA says. — Christopher Hollis
A patent reform bill may compete for attention in the next Congress because of pressure from the biotechnology industry and other interest groups to pass follow-on biologic legislation, an expert says.
Patent reform has faced a bumpy road in the 110th Congress. The Patent Reform Act of 2007, S. 1145, was introduced by Sen. Patrick Leahy (D-Vt.), chairman of the Senate Judiciary Committee, in April 2007. Although the House passed a version of the bill, H.R. 1908, last year, it was placed on the Senate Legislative Calendar under General Orders in January, but no other action has been taken (DID, Nov. 16, 2007).
President-elect Obama has expressed support for significant patent reform, saying “timely, high-quality patents” are essential for the U.S. to be competitive globally.
At the same time, there is a strong push to pass a follow-on biologics bill to provide incentives for biotechnology companies, Jeffrey Kushan, a partner at Sidley Austin, said at the BNA’s Pharmaceutical Patent Laws: A Prescription for Success in Challenging Times conference Wednesday.
While support for a patent bill is strong on both sides of the aisle, there are issues left to be resolved, Kushan said. Setting standards for awarding patent damages is one decision that may be decided by the courts, he added.
The Commerce Department weighed in on this topic earlier this year when it notified the Judiciary Committee that the damages section, which would codify reasonable royalty awards in patent litigation, would seriously harm the U.S. intellectual property system (DID, Feb. 6).
In a Feb. 4 letter to Leahy and other committee members, Commerce says the bill’s damages provision “will create more problems than it solves.”
Other issues include the creation of a more vigorous validity review procedure at the Patent and Trademark Office, implementation of a first-to-file system to support patent harmonization and worksharing, and reform of the inequitable conduct standard, Kushan said.
Kushan also pointed out that past patent reform bills have taken a long time. The current effort has lasted five years. — Elizabeth Jones
After reviewing data on a potentially increased risk of atrial fibrillation in patients receiving bisphosphonates to treat bone disease, the FDA advises physicians not to change their prescribing habits.
The safety review was announced Oct. 1, 2007, when the agency asked Merck, Roche, Novartis and Procter & Gamble for placebo-controlled clinical trial data on the potential for an increased risk of atrial fibrillation in patients taking bisphosphonates. Sponsors submitted data on 19,687 bisphosphonate patients and 18,358 patients taking placebos who were followed for six months to three years.
“No clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed,” the FDA says in a statement. The agency says it is considering whether to seek additional epidemiological studies and will keep monitoring postmarket reports of arrhythmia in bisphosphonate patients.
The bisphosphonates on the market include:
The drugs’ indications include osteoporosis, Paget’s disease and bone cancer, according to the FDA. Generic Aredia, from Barr Pharmaceuticals’ subsidiary Pliva-Lachema, was approved to treat myeloma bone disease this year (DID, Sept. 3).
The FDA’s early communication is available at www.fda.gov/cder/drug/early_comm/bisphosphonates.htm. — Theresa Barry
Nonvoting industry representatives may be nominated in the next month to sit on three CBER advisory committees.
The panels are the Cellular, Tissue and Gene Therapies Advisory Committee, the Vaccines and Related Biological Products Advisory Committee and the Transmissible Spongiform Encephalopathies Advisory Committee.
Candidates may nominate themselves or be nominated by an industry organization. Groups that want to participate in selecting the nonvoting members are invited to write a letter to the FDA expressing their interest.
Letters and nominations are due by Dec. 13. The CBER notice can be viewed at www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-N-0581-n.pdf. — Martin Gidron
Contract manufacturer PrimaPharm was cited by the FDA for GMP violations related to its sterile drug products.
The company did not establish and follow written procedures to prevent microbiological contamination of sterile drugs, according to the FDA’s Oct. 31 warning letter.
Media fills used to validate unidentified processes were deficient, and the environmental monitoring program did not include sampling of critical surfaces, the FDA says. Procedures for clean room operations were cited as well.
“In light of the significant problems you encountered with the control of the [redacted] facility, … as well as the significant GMP observations documented during the current inspection, we are concerned about your incomplete investigations and your conclusions regarding the media fill failure,” the letter continues.
“These deviations raise significant concerns with sterility assurance of products that were produced under these conditions,” the letter says. “While we acknowledge that you are taking steps to address many of these deficiencies, please provide your rationale for the distribution of products potentially implicated by the media fill contamination and the significant cGMP violations.”
The company was warned about marketing two unapproved new drugs — their names were redacted from the letter. In addition, the company marketed OTC drugs without an approved application.
The letter, which was posted to the FDA’s website Wednesday, follows a May 1–14 inspection of the company’s San Diego facility. It is available at www.fda.gov/foi/warning_letters/s6999c.pdf. — Christopher Hollis
Sens. Mike Enzi (R-Wyo.) and Tom Coburn (R-Okla.) of the Committee on Health, Education, Labor and Pensions have sent letters to FDA Commissioner Andrew von Eschenbach and HHS Inspector General Daniel Levinson asking them to look into the agency’s sole-source contract with a public relations firm.
The senators’ letters follow similar letters sent earlier this year by House lawmakers. In April, House Energy and Commerce Committee chairman John Dingell (D-Mich.) and Oversight and Investigations Subcommittee chairman Bart Stupak (D-Mich.) wrote von Eschenbach asking for records and information about the FDA’s contracts with public relations firms (DID, April 24).
The FDA replied in August, telling the committee that the agency had contracted with Qorvis, a Washington, D.C., company acting as a subcontractor for Alaska Newspapers, Inc. As a result, three separate investigations were launched into the agency’s award of the contract because it may have skirted government contracting rules (DID, Oct. 3).
The senators ask von Eschenbach for detailed information by Dec. 1. They request that Levinson investigate “the actions and communications of FDA officials with respect to Alaska Newspapers and Qorvis” and apprise them of progress in periodic status reports and updates.
The senators’ statement and letters are available at www.fdanews.com/ext/files/MikeEnzi111208.pdf. — David Grant
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