Regulatory Affairs Syndicator

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Characterization of the protective T-cell response generated in CD4-deficient mice by a live attenuated Mycobacterium tuberculosis vaccine.

Immunology. 2006 Oct 31;

Authors: Derrick SC, Evering TH, Sambandamurthy VK, Jalapathy KV, Hsu T, Chen B, Chen M, Russell RG, Junqueira-Kipnis AP, Orme IM, Porcelli SA, Jacobs WR, Morris SL

The global epidemic of tuberculosis, fuelled by acquired immune-deficiency syndrome, necessitates the development of a safe and effective vaccine. We have constructed a DeltaRD1DeltapanCD mutant of Mycobacterium tuberculosis (mc(2)6030) that undergoes limited replication and is severely attenuated in immunocompromised mice, yet induces significant protection against tuberculosis in wild-type mice and even in mice that completely lack CD4(+) T cells as a result of targeted disruption of their CD4 genes (CD4(-/-) mice). Ex vivo studies of T cells from mc(2)6030-immunized mice showed that these immune cells responded to protein antigens of M. tuberculosis in a major histocompatibility complex (MHC) class II-restricted manner. Antibody depletion experiments showed that antituberculosis protective responses in the lung were not diminished by removal of CD8(+), T-cell receptor gammadelta (TCR-gammadelta(+)) and NK1.1(+) T cells from vaccinated CD4(-/-) mice before challenge, implying that the observed recall and immune effector functions resulting from vaccination of CD4(-/-) mice with mc(2)6030 were attributable to a population of CD4(-) CD8(-) (double-negative) TCR-alphabeta(+), TCR-gammadelta(-), NK1.1(-) T cells. Transfer of highly enriched double-negative TCR-alphabeta(+) T cells from mc(2)6030-immunized CD4(-/-) mice into naive CD4(-/-) mice resulted in significant protection against an aerosol tuberculosis challenge. Enriched pulmonary double-negative T cells transcribed significantly more interferon-gamma and interleukin-2 mRNA than double-negative T cells from naive mice after a tuberculous challenge. These results confirmed previous findings on the potential for a subset of MHC class II-restricted T cells to develop and function without expression of CD4 and suggest novel vaccination strategies to assist in the control of tuberculosis in human immunodeficiency virus-infected humans who have chronic depletion of their CD4(+) T cells.

PMID: 17076705 [PubMed - as supplied by publisher]

Focus on Management of Pacemaker and ICD Advisories, Recalls, and Alerts.

Curr Treat Options Cardiovasc Med. 2006 Sep;8(5):347-52

Authors: Amin MS, Ellenbogen KA

Because the number of implantable cardiac devices has dramatically increased, device alerts and advisories have become a part of routine clinical practice. When a physician is faced with the management of a patient with an implanted device that has been the subject of a recall or advisory, the major concern facing the clinician is how to manage the patient and whether the device needs to be replaced. A rational approach to evaluating patients with a device or lead that is the subject of a US Food and Drug Administration advisory requires evaluating the competing risks of elective device or lead replacement versus keeping the recalled device or lead in place. It is important to keep in mind that the risks of replacing devices are not insignificant and may outweigh the risks of death from device malfunction. Ultimately, this decision should be based on the estimated device (lead) malfunction rate, device (lead) dependency, and an individual center’s procedural risk for complications from generator (lead) removal, and should also factor in patient preferences.

PMID: 16939672 [PubMed - in process]

Recalls and safety alerts affecting automated external defibrillators.

JAMA. 2006 Aug 9;296(6):655-60

Authors: Shah JS, Maisel WH

CONTEXT: Automated external defibrillators (AEDs) play a key role in the community resuscitation of persons with cardiac arrest and are of proven clinical benefit. Although AEDs are complex medical devices designed to function during life-threatening emergencies, little is known about their reliability. OBJECTIVES: To determine the number and rate of AED recalls and safety alerts, to identify trends in these rates, and to identify the types of malfunctions prompting AED and AED accessory advisories. DESIGN AND SETTING: Analysis of weekly US Food and Drug Administration (FDA) Enforcement Reports between January 1996 and December 2005 was performed to identify all recalls and safety alerts (collectively referred to as “advisories”) involving AEDs and AED accessories. Confirmed AED device malfunctions were identified by reviewing AED-related adverse events reported to the FDA. MAIN OUTCOME MEASURES: Number of AEDs and AED accessories subject to FDA recall or safety alert between January 1996 and December 2005; annual AED advisory rates; and number of confirmed fatal AED-related device malfunctions reported to the FDA. RESULTS: During 2.78 million AED device-years of observation, 52 advisories (median [25th and 75th percentiles], 4.5 [3.0 and 5.0] per year) affecting 385,922 AEDs and AED accessories were issued. The mean (SE) annual number of AEDs affected by advisories was 5.1 (1.5) devices per 100 AED device-years. Overall, 21.2% of AEDs distributed during the study period were recalled, most often because of electrical or software problems. The AED advisory rate did not significantly increase during the study period, although the annual number of AED advisories (P for trend =.02) and AED advisory devices (P for trend = .01) did increase. Confirmed fatal AED-related device malfunctions occurred in 370 patients. CONCLUSIONS: Automated external defibrillators and AED accessory advisories occur frequently and affect many devices. Actual AED malfunctions do occur occasionally, although the number of observed malfunctions is small compared with the number of lives saved by these important devices. As the prevalence of AEDs continues to increase, the number of devices affected by advisories can also be expected to increase. Efforts should be directed at developing a reliable system to locate and repair potentially defective devices in a timely fashion.

PMID: 16896108 [PubMed - in process]

Brief report: investigation into recalled human tissue for transplantation–United States, 2005-2006.

MMWR Morb Mortal Wkly Rep. 2006 May 26;55(20):564-6

Authors:

On September 29, 2005, a human tissue-processing company discovered inaccuracies in donor records forwarded from a tissue-recovery firm and notified the Food and Drug Administration (FDA). An FDA investigation determined that the recovery firm, Biomedical Tissue Services, Ltd. (BTS) (Fort Lee, New Jersey), recovered tissues from human donors who might not have met donor eligibility requirements and who were not screened properly for certain infectious diseases. In October 2005, BTS and the five processors that had received the tissues, working with FDA, issued a recall for all tissues recovered by BTS. The continuing FDA investigation determined that information for some donors (e.g., cause, place, or time of death) was not consistent with death certificate data obtained from the states where the deaths occurred. The investigation also determined that BTS had failed to recover tissues in a manner that would prevent contamination or cross-contamination and failed to control environmental conditions adequately during tissue recovery. These failures were violations of the Current Good Tissue Practice Rules (effective May 25, 2005), which require manufacturers to recover, process, store, label, package, and distribute human cells, tissue, and cellular and tissue-based products (HCT/Ps) to prevent introduction, transmission, or spread of communicable diseases. In January 2006, FDA ordered BTS to cease manufacturing and to retain all HCT/Ps.

PMID: 16723969 [PubMed - indexed for MEDLINE]

Acoustic-resonance spectrometry as a process analytical technology for rapid and accurate tablet identification.

AAPS PharmSciTech. 2006;7(1):E25

Authors: Medendorp J, Lodder RA

This research was performed to test the hypothesis that acoustic-resonance spectrometry (ARS) is able to rapidly and accurately differentiate tablets of similar size and shape. The US Food and Drug Administration frequently orders recalls of tablets because of labeling problems (eg, the wrong tablet appears in a bottle). A high-throughput, nondestructive method of online analysis and label comparison before shipping could obviate the need for recall or disposal of a batch of mislabeled drugs, thus saving a company considerable expense and preventing a major safety risk. ARS is accurate and precise as well as inexpensive and nondestructive, and the sensor is constructed from readily available parts, suggesting utility as a process analytical technology (PAT). To test the classification ability of ARS, 5 common household tablets of similar size and shape were chosen for analysis (aspirin, ibuprofen, acetaminophen, vitamin C, and vitamin B12). The measures of successful tablet identification were intertablet distances in nonparametric multidimensional standard deviations (MSDs) greater than 3 and intratablet MSDs less than 3, as calculated from an extended bootstrap error-adjusted single sample technique. The average intertablet MSD was 65.64, while the average intratablet MSD from cross-validation was 1.91. Tablet mass (r (2) = 0.977), thickness (r (2) = 0.977), and density (r (2) = 0.900) were measured very accurately from the AR spectra, each with less than 10% error. Tablets were identified correctly with only 250 ms data collection time. These results demonstrate that ARS effectively identified and characterized the 5 types of tablets and could potentially serve as a rapid high-throughput online pharmaceutical sensor.

PMID: 16584156 [PubMed - in process]

The Progressive Era.

J Am Coll Dent. 2005;72(2):33-8

Authors: Chambers DW

The American College of Dentists was founded in 1920 for the purpose of encouraging young dentists to continue study and to apply science to their practices. This ideal emerged in the Progressive Era, which lasted roughly from 1895 to 1920. The animating spirit of this period was that the human condition could be improved and that the way to achieve this was through science and the use of experts working together. The Progressive Era saw inventions, such as automobiles and airplanes, telephone and radio, that required mass production and brought people together. It also spawned many political and legislative innovations that we now take for granted. Among these are the Food and Drug Administration, the Department of Commerce, and the Federal Trade Commission. Workers’ compensation and other social protections were introduced, as were city commissions; the income tax; women’s suffrage; and initiative, referendum, and recall. Medicine, for the first time, became an effective way to treat disease as it developed a scientific foundation.

PMID: 16350929 [PubMed - in process]

FDA asks LyphoMed to recall intravenous solution.

Mod Healthc. 1988 Jul 29;18(31):5

Authors: Wagner M

PMID: 10288204 [PubMed - indexed for MEDLINE]

Adverse drug events: identification and attribution.

Drug Intell Clin Pharm. 1987 Nov;21(11):915-20

Authors: Rogers AS

The definition of an adverse drug event should be tailored to one’s purpose in examining the incident. Although the more specific of these definitions is required for scientific evaluation of the link between drug and event, other less stringent definitions are usually adequate for clinical purposes. Knowledge about the safety profile of a drug in humans is limited at the time of marketing. The mechanisms for supplementing safety data during postmarketing include (1) the Spontaneous Reporting System maintained by the Food and Drug Administration, (2) formal projects to assemble safety data on larger or more complex populations, and (3) formal projects designed to answer specific research questions. Judgments about attribution can be no better than the data that support them. The criteria applied by the clinician to the individual adverse drug experience to determine association differ from those required to establish causation based on epidemiologic evidence. In most situations, regulatory action on drug recall should be based on epidemiologic evidence. This article will discuss the choice of a definition for an adverse drug event, examine the extent and nature of the safety data assembled on a drug at the time it is marketed, propose the best methods for collecting additional information after marketing, and designate factors to be considered in judging a drug to be causally related to an adverse event.

PMID: 3678067 [PubMed - indexed for MEDLINE]

The Dalkon Shield in perspective.

Med Law. 1986;5(1):35-44

Authors: Pendergast P, Hirsh HL

PMID: 3515100 [PubMed - indexed for MEDLINE]

Establishing control through standardized recall procedures.

Hosp Mater Manage Q. 1985 Aug;7(1):56-65

Authors: Kovacs GL

PMID: 10278336 [PubMed - indexed for MEDLINE]

Policy and procedure manual. Drug recall program.

Curr Concepts Hosp Pharm Manage. 1984;6(3):19

Authors:

PMID: 10267189 [PubMed - indexed for MEDLINE]

A medical device recall and reporting system. Guideline report.

Hosp Technol Ser. 1983 Dec;2(32):1-21

Authors: Alder HC

PMID: 10267947 [PubMed - indexed for MEDLINE]

The Food and Drug Administration’s role in the canned salmon recalls of 1982.

Public Health Rep. 1983 Sep-Oct;98(5):412-5

Authors: Hayes AH

The Alaska salmon industry conducted 9 recalls of 7 3/4-oz cans of salmon in 1982 after a 7 3/4-oz can of Alaskan salmon was implicated in illness and one death in Belgium from Clostridium botulinum type E toxin. By the code number on the can, the Food and Drug Administration (FDA), Seattle District, traced it to a specific salmon packer. Subsequently, the FDA received a report about a defect in the can. Investigation of the salmon packer’s plant by the Agency revealed that the equipment used at the plant to reform the cans–which arrived at the cannery in a nearly flattened state–might have been responsible for the defect. The death and illness in Belgium, combined with the results of the FDA inspection of the plant implicated in the Belgian incident, provided strong evidence of the existence of a hazardous situation that might have widespread adverse health effects. The Food and Drug Administration therefore requested the firm to recall its 1980 and 1981 production of salmon packaged in 7 3/4-oz cans. The Agency then began an investigation of all U.S. salmon packed inn cans of this size that had been reformed on the equipment implicated in the can defect. Of 300,000 cans examined, 22 with the defect were found. As additional firms were identified as having used the defective cans, subsequent recalls were initiated.

PMID: 6414026 [PubMed - indexed for MEDLINE]

Guidelines for recall of blood from AIDS donors? FDA says no.

Med World News. 1983 Aug 22;24(16):24

Authors:

PMID: 10261844 [PubMed - indexed for MEDLINE]

The Dalkon Shield debate.

Conn Med. 1983 Mar;47(3):138-41

Authors: Goodhue PA

PMID: 6851548 [PubMed - indexed for MEDLINE]