Vol. 9 No. 108
The FDA is drafting a proposed rule that would extend its authority so that clinical investigators disqualified for one type of investigation, such as drugs, would be ineligible to conduct work on any other FDA-regulated product, including, but not limited to drugs, biologics and devices.
The proposed rule, expected to be ready by the end of the year, is designed “to help ensure adequate protection of research subjects and the quality and integrity of data submitted to FDA,” according to a statement by the agency’s Office of Good Clinical Practice.
The proposed rule will address criticisms outlined in a Government Accountability Office (GAO) report that recommended the FDA amend regulations to extend its disqualification authority and speed up the disqualification and debarment process (DID, Oct. 23, 2009).
Debarment and disqualification — to remove researchers from conducting clinical testing of new drugs and devices — are two separate actions available to the FDA for clinical investigators and companies accused of misconduct. The agency may also ban, or “debar” from the drug industry individuals and companies convicted of certain felonies or misdemeanors related to drug products.
But that authority does not extend to devices, at least not yet. Congress must give the FDA the authority to debar certain individuals and companies to keep them from working on or with FDA-regulated devices.
Disqualification Procedures Guidance Released
In a related matter, the FDA issued a guidance to help inform institutional review boards (IRBs), clinical investigators and sponsors about the agency’s new and updated procedures for disqualifying a clinical investigator.
View the draft of the proposed rule, “Disqualification of a Clinical Investigator,” at www.reginfo.gov/public/do/eAgendaViewRule?pubId=201004&RIN=0910-AG49.
View the FDA guidance, “Clinical Investigator Administrative Actions – Disqualification,” at www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM214008.pdf. — LaCrisha Butler
A federal appeals court has revived two product liability suits against GlaxoSmithKline (GSK) and Wyeth in the wake of the U.S. Supreme Court’s decision in Wyeth v. Levine.
Both lawsuits had been dismissed by U.S. District Courts on the grounds that federal law preempted failure-to-warn claims against the companies. But the U.S. Court of Appeals for the Tenth Circuit reversed those decisions and remanded the cases back to the district courts Wednesday, saying that following Wyeth v. Levine, the companies must provide clear evidence that the FDA would have rejected labeling changes had they been proposed.
The case against Wyeth was brought by a plaintiff who said the company failed to adequately label its antidepressant Effexor (venlafaxine HCl) to warn of suicide risk, and that this failure to warn caused her husband’s suicide in 2002 while he was taking the drug.
This was similar to the case against GSK, which alleged that the company’s failure to adequately label its antidepressant Paxil (paroxetine HCl) to warn of suicide risk caused a suicide attempt by one of the plaintiffs.
“After Levine, GSK must demonstrate that federal labeling requirements made it impossible to meet its state law duty to warn by proving that there was ‘clear evidence’ that the FDA would have rejected GSK’s labeling change had it unilaterally strengthened Paxil’s warning label using the [changes being effected] supplement,” the appeals court says in its ruling.
The district courts should allow the parties to submit additional evidence and then reconsider the rulings in light of Levine’s new clear evidence standard, the appeals court says.
GSK intends to prove that its case meets that standard, Sarah Alspach, a spokeswoman for GSK, told DID. The company “looks forward to presenting to the district court why the substantial regulatory history involved meets the clear evidence standard of Wyeth v. Levine,” Alspach said.
A spokesman for Pfizer, which now owns Wyeth, did not respond by press time to a request for comment.
The appeals court’s rulings in Annabel Dobbs v. Wyeth Pharmaceuticals and Candace Miller and George Miller v. Smithkline Beecham Corporation d/b/a GlaxoSmithKline et al. were filed June 2. — David Belian
The House Committee on Oversight and Government Reform is again expanding its investigation into the McNeil Consumer Healthcare plant linked to recent pediatric drug recalls, to include last week’s recall of PediaCare products manufactured at the plant.
Chairman Edolphus Towns (D-N.Y.) has questions about the conditions of the Johnson & Johnson (J&J) subsidiary’s Fort Washington, Pa., plant, which manufactured PediaCare, a children’s cough and cold medication, for Blacksmith Brands.
Blacksmith announced the precautionary recall last Friday, and the House committee is asking Blacksmith’s CEO to provide details about the recall, including records of communications between Blacksmith, McNeil, J&J and the FDA.
The recall was not initiated as a result of adverse event reports or complaints, but because tiny particles have been found in other products manufactured at the McNeil plant, Blacksmith has said.
In a June 2 letter to Blacksmith’s CEO, Towns asks:
Towns requests the information by June 10.
This is the second expansion of the committee’s ongoing investigation into McNeil-related recalls in a little more than a week.
Recently, the committee expanded its investigation into recent pediatric drug recalls to include a 2008 “phantom recall” of Motrin (DID, June 2). The committee asked J&J for the names and contact information of employees involved in a decision to remove defective Motrin from retail outlets in 2008, instead of conducting a recall of the product. — April Hollis
The FDA has flexed its recently acquired enforcement muscles once again, forcing a label change for the long acting beta-2 agonist (LABA) class of drugs in an effort to reduce their use without another asthma controller medicine such as an inhaled corticosteroid.
In February, the agency issued a request for companies to change the labels themselves after the FDA’s analyses of studies showed an increased risk of severe exacerbation of asthma symptoms leading to hospitalizations when LABAs are used alone (DID, Feb. 19).
The label change applies to LABA-only drugs such as GlaxoSmithKline’s (GSK) Serevent (salmeterol xinafoate) and Novartis’ Foradil (formoterol fumarate) and drug-drug combinations containing LABAs — GSK’s Advair (fluticasone propionate/salmeterol xinafoate) and AstraZeneca’s Symbicort (budenoside/formoterol fumarate dihydrate).
Some drugmakers did not heed the FDA’s call, according to agency officials, and had been negotiating label modifications. On Wednesday, the agency finalized a boxed warning and risk evaluation and mitigation strategy for the class that includes a revised medication guide written for patients and a plan to educate healthcare professionals about the appropriate use of LABAs.
GSK said Wednesday that it had received a letter from the FDA notifying it of the label mandate. “The letter concludes discussions between GSK and the agency …,” the company said, adding that “Advair and Serevent remain important treatment options for appropriate patients with asthma and [chronic obstructive pulmonary disease] (COPD).”
Product labels must now state that LABAs should not be used alone without a long-term asthma controller medication, such as an inhaled corticosteroid, and should not be used in patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids. Children and adolescents who require use of LABAs with their inhaled corticosteroid treatment should only use combination products, containing LABAs and inhaled corticosteroids.
In addition, LABAs:
The new recommendations do not apply to the use of LABAs for COPD.
The FDA held a joint advisory committee meeting in March at which members voiced support for a 12-month postmarket safety study in asthma patients for all members of the LABA class.
The Food and Drug Amendments Act of 2007 gave the FDA the power to mandate drug label changes for safety reasons. — LaCrisha Butler
Sagent Pharmaceuticals and Claris Lifesciences are still working to get to the root cause of nonsterility issues with recalled metronidazole, as Claris moves to recall certain strengths of its ciprofloxacin and ondansetron as well.
Claris, which manufactures metronidazole for Sagent, and separately manufactures the other two products, is conducting the recall because of possible contamination due to the products’ packaging integrity, the FDA said this week.
The recall affects all lots of Claris’ antibiotic ciprofloxacin injection 200 mg/100 mL and 400 mg/200 mL, antimicrobial metronidazole injection 500 mg/100 mL and nausea drug ondansetron injection 32 mg/50 mL.
Claris is not aware of any adverse patient events resulting from the products and is continuing its investigation, the FDA said. — April Hollis
Cephalon has abandoned an effort to get its excessive sleepiness treatment Nuvigil approved as an adjunctive schizophrenia therapy following the failure of a Phase II trial.
The company said Wednesday that the trial did not meet its primary endpoint, which was to lessen the severity of the negative symptoms of schizophrenia compared to placebo in a 24-week study. Nuvigil was used as an add-on to an antipsychotic medication (olanzapine, oral risperidone or paliperidone) in the study.
The FDA approved Nuvigil (armodafinil) in June 2007 to improve wakefulness in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder or narcolepsy.
Cephalon also said it will continue with plans for a Phase III trial evaluating Nuvigil in bipolar depression and excessive sleepiness resulting from traumatic brain injury.
In addition, the company is continuing discussions with the FDA on its sNDA for Nuvigil as a treatment for jet lag. The FDA issued a complete response letter March 29 on that application. The company had a special protocol assessment agreement with the agency to evaluate the experience of a typical eastbound airline traveler, and reached statistical significance on both primary endpoints, it said. But the FDA action letter raised questions about the robustness of patient assessment findings. — Jonathan Block
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