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Background. Palivizumab is a US Food and Drug Administration–approved monoclonal antibody for the prevention of respiratory syncytial virus (RSV) lower respiratory disease in high-risk infants. Motavizumab, derived from palivizumab with enhanced antiviral activity, has recently been tested in humans. Although palivizumab escape mutants have been generated in the laboratory, the development of resistant RSV in patients receiving palivizumab has not been reported previously.Methods. We generated palivizumab and motavizumab escape mutants in vitro and examined the development of resistant mutants in RSV-breakthrough patients receiving immunoprophylaxis. The effect of these mutations on neutralization by palivizumab and motavizumab and in vitro fitness was studied.Results. Antibody-resistant RSV variants selected in vitro had mutations at position 272 of the fusion protein, from lysine to asparagine, methionine, threonine, glutamine, or glutamate. Variants containing mutations at positions 272 and 275 were detected in breakthrough patients. All these variants were resistant to palivizumab, but only the glutamate variant at position 272 demonstrated resistance to motavizumab. Mixtures of wild-type and variant RSV soon lost the resistant phenotype in the absence of selection.Conclusions. Resistant RSV variants were detected in a small subset (∼5%) of RSV breakthrough cases. The fitness of these variants was impaired, compared to wild-type RSV. [ABSTRACT FROM PUBLISHER]

The article looks at the U.S. Food and Drug Administration (FDA). According to FDA's acting commissioner Andrew von Eschenbach, the FDA must change the way it examines and approves new drugs and medical devices. The article discusses FDA's failure to act on the application of the morning after emergency contraceptive, the FDA's Critical Path Initiative, legislation in U.S. Congress that would allow more changes in drug-approval process of the FDA, known as the "Access, Compassion, Care, and Ethics for Seriously III Patients Act," and a report by the U.S. Government Accountability Office that criticized the FDA's monitoring of postmarket drug safety.

Reports that the U.S. Food and Drug Administration advisory panel recommended that GlaxoSmithKline be allowed to market alosetron, a serotonin antagonist, for irritable bowel syndrome (IBS). Discussion of side effects and deaths due to alosetron, which was previously withdrawn from the market; Demand of IBS patients for access to the drug; Provision that there be significant restrictions on who can prescribe the drug and that patients be carefully followed.

The article details a lawsuit filed by the Treatment Action Group and the Global Health Justice Partnership with the U.S. District Court of Connecticut on June 25, 2015 to seek access to clinical data submitted to the U.S. Food and Drug Administration for the approval of the hepatitis C drug sofosbuvir.

Reports on the US Food and Drug Administration's (FDA) charge that Upjohn Co. committed a misconduct when it tried to conceal dangerous side-effects of the sleeping pill Halcion or triazolam; Conduction of the investigation in 1991 and 1992; Summary of the FDA's report; Marketing of Halcion; Other charges by the FDA against Upjohn; Reactions of Upjohn officials to the FDA's report.

The article looks at Andrew von Eschenbach, who is the acting commissioner of the U.S. Food and Drug Administration (FDA). Prior to the FDA, von Eschenbach was the director of the U.S. National Cancer Institute. The article discusses von Eschenbach's program known as the Oncology Biomarker Qualification Initiative, medical breakthroughs in cancer research, von Eschenbach's belief that cancer will become a manageable chronic disease, and his attempts to quicken the discovery, development, and availability of new drugs and treatments.

Reports that the U.S. Food and Drug Administration has decided to reapprove the use of alosetron hydrochloride to treat irritable bowel syndrome. Controversy about the drug, which was pulled from the market after reports of dangerous side effects; Restrictions on the use of the drug; Response of the drug's manufacturer, GlaxoSmithKline.

Discusses rules proposed by the United States Food and Drug Administration (FDA) that would require researchers doing human trials of gene therapies and xenotransplantation to post safety information about the treatment on the agency's web site. Hopes that the action will restore public confidence in the therapies after a series of scandals in 2000, including the death of Jesse Gelsinger; Reaction of the consumer advocacy group Public Citizen and the medical and pharmaceutical communities.

Reports on the concern over the use of psychotropic drugs to treat young children with attention deficit hyperactivity disorder (ADHD) in the United States. Efforts of First Lady Hillary Rodham Clinton to launch an initiative to improve care of children with ADHD; Four federal programs included in the initiative; Concern that psychotropic drugs are being overprescribed.

Reports on the launch of two initiatives by the United States Food & Drug Administration and the National Institutes of Health aimed to protect patients participating in gene-therapy trials. Basis of the programs in light of the death of test patient Jesse Gelsinger in September 1999; Adjustment of government regulations of gene therapy by way of the Gene Therapy Clinical Trial Monitoring Plan; Launch of public meeting among researchers to discuss safety during the Gene Transfer Safety Symposia.

Reports on the rejection by the United States Food and Drug Administration (FDA) of arguments made by the University of Pennsylvania in defense of its gene-therapy program. Shutdown of the trial by the FDA after the death of Jesse Gelsinger and the discovery of several protocol violations; Basis of the university's response to allegations over questionable safety standards; Demands of the FDA before the program could be reinstituted.

Reports on the status of experiments being conducted by Vascular Genetics of Durham, North Carolina. Intent of experiments which involve vascular gene-therapy; United States Food and Drug Administration (FDA) request that the company halt one of its trials; Reasons for the FDA request including the death of a young man undergoing experimental gene therapy in 1999; Scrutiny of the gene-therapy researchers in the US.

Reports that United States Food and Drug Administration officials said there is no evidence that an experimental gene therapy vaccine given to children with neuroblastoma was contaminated with HIV or hepatitis C virus (HCV). St. Jude Children's Research Hospital in Memphis, Tennessee sending vaccine material for testing; Concern about protocol violations.

Reports the ruling by a United States federal judge curtailing the regulatory powers of the US Food and Drug Administration (FDA). Licensing approvals for drugs; FDA regulations forbidding drug companies to discuss off-label use in promotional efforts; Details of the ruling.

Looks at the approval of all-trans retinoic acid (ATRA, tretinoin) by the United States' Food and Drug Administration for the treatment of acute promyelocytic leukaemia (APL).

Reports that the United States' Food and Drug Administration has approved alendronate to treat postmenopausal osteoporosis and Paget's disease. Marketing by Merck and Co as Fosamax; Characteristics of alendronate.

Reports that a US Food and Drug Administration (FDA) advisory committee has recommended that the agency permit the marketing of two computerized Pap smear screening devices. AutoPap developed by NeoPath Inc.; PAPNET by Neuromedical Systems Inc.; Purpose of devices.

Reports on the petition filed by the Center for Reproductive Law and Policy before the Food and Drug Administration on the need for instructions labels for six brands of contraceptives. Instruction on use as postcoital contraceptives; Impairment of the movement of the ovum down the fallopian tube; Interference with the development of the uterine lining.

Reports on legal battles between the American Government and the tobacco industry. Department of Justice's review of evidence suggesting illegal concealment of information on the hazards of cigarette smoking; Food and Drug Administration Commissioner David Kessler's campaign to convince Congress on the tobacco industry's intentional use of nicotine; Suit filed by the industry against the Environmental Protection Agency.

Reports on the approval of pulmozyme, an aerolised recombinant human DNase, for the treatment of cystic fibrosis by the United States Food and Drug Administration. Improvement of viscoelasticity of mucous secretions of cystic fibrosis patients; Drug manufacturer's marketing applications for Canada and Europe.

States a United States District Court in Utah lifted a ban on a product being sold as dietary supplement. The US Food and Drug Administration (FDA) contending Cholestin is an unapproved drug; The supplement, marketed by Pharmanex, containing a red-yeast rice; The issue of the product's fermentation process; Background on Pharmanex's lawsuit against the FDA.