Drug Administration Manufacturer Research Articles

Lessons From the Failure and Recall of an Implantable Cardioverter-Defibrillator

Multiple clinical trials have shown that a properly functioning implantable cardioverter-defibrillator (ICD) is capable of interrupting sudden death caused by ventricular tachyarrhythmias. Unfortunately, ICDs are complex medical devices, and they do not always perform as expected. For example, only 5% of ICD batteries last >7 years, and most dual-chamber ICD models must be replaced for battery depletion every 3 to 5 years.1 Normal battery depletion, however, is reliably predicted by routine follow-up methods before an ICD fails. In contrast, electronic malfunctions are unpredictable and may not be detected by standard follow-up techniques before an ICD is unable to deliver effective therapy. Thus, sudden cardiac arrest or death may be the first and only sign that an ICD has failed.2 Recently, we reported the death of a 21-year-old patient who received a Prizm 2 DR model 1861 ICD pulse generator (Guidant, Inc) in 2001 to prevent sudden cardiac death resulting from hypertrophic cardiomyopathy.3 In March 2005, this young man experienced a witnessed arrest and could not be resuscitated. His ICD was returned to Guidant, which found that the device had failed during the delivery of a shock. The cause of failure was massive electronic damage caused by electrical overstress that occurred when a short circuit developed between a high-voltage wire and a tube used to test the housing during manufacturing (see the Figure). At the time of our patient’s death, Guidant had knowledge of 25 similar Prizm 2 DR model 1861 failures in patients, 3 of whom had required rescue defibrillation. Indeed, Guidant had first observed this mode of failure 3 years earlier, in February 2002, when 2 returned Prizm 2 DR pulse generators exhibited the same short circuiting that caused our patient’s device to fail. Guidant was sufficiently concerned about these failures that manufacturing changes were made …

Vertebral Augmentation and the Limits of Interpreting Complications Reported in the Food and Drug Administration Manufacturer and User Facility Device Experience Database

We are honored to have been asked to provide commentary on the accompanying perspective by Nussbaum and coauthors ( 1 Nussbaum DA Gailloud P Murphy K A review of complications associated with vertebroplasty and kyphoplasty as reported to the Food and Drug Administration medical device related web site. J Vasc Interv Radiol. 2004; 15: 1185-1192 Abstract Full Text Full Text PDF PubMed Scopus (251) Google Scholar ) and to be allowed to share our collective comments concerning its content and scientific validity. The authors of this review include spinal surgeons, radiologists, an interventional physiatrist, and a biostatistician. Given the nature of the analyses and conclusions of this article, we considered it appropriate to add our collective opinions regarding some of the significant issues related to vertebroplasty, kyphoplasty, and the treatment of symptomatic vertebral compression fractures.

Deaths associated with implantable cardioverter defibrillator failure and deactivation reported in the United States Food and Drug Administration Manufacturer and User Facility Device Experience Database

The aim of this study was to understand the causes of implantable cardioverter defibrillator (ICD) failure and complications so that adverse events, including unnecessary death, can be prevented. Sudden death may occur if an ICD fails to treat life-threatening ventricular arrhythmias. The United States Food and Drug Administration Manufacturer and User Facility Device Experience Database was searched for ICD devices and the search term "death." The search yielded 212 death events involving 100 ICD pulse generator and lead models from five manufacturers. These death events were associated with (A) ICD devices for which pulse generator interrogation data and/or the results of the manufacturers analysis of returned devices were available; (B) ICD devices for which neither interrogation data nor the results of the manufacturer's analysis were reported; and (C) normally functioning ICDs that had been deactivated. (A) A total of 103 (69%) of 150 death events were associated with defective pulse generators or high-voltage leads. Most (34/42 [81%]) apparently sudden or arrhythmic death events were associated with high-voltage lead failure; other deaths were related to pulse generator failure (8/42 [19%]) caused by electronic component defects. (B) A total of 21 of 51 death events were related to a manufacturer's recall; all deaths were arrhythmic but without allegation of device failure. (C) Eleven death events occurred in patients whose pulse generators were found to be off or deactivated; these devices appeared to have been deactivated accidentally or by exposure to magnetic fields, or they were not reactivated after elective surgery. ICD device failure and unintended pulse generator deactivation have resulted in unnecessary deaths. Although these deaths may be infrequent, improved devices and follow-up techniques are needed. The magnet deactivation feature probably is unsafe, and health professionals and patients should be cautioned.

An Analysis of Home and Hospital Medical Device Incidents in the MAUDE Database

A review of the U.S. Food and Drug Administration's Manufacturer and User Facility Device Experience Database (MAUDE) was performed to identify medical device incident trends relating to the type of device involved, incident location, injury severity, the nature and/or cause of the event, and human factors issues involved. A total of 317,931 medical device incident reports submitted by manufacturers between the years 1997 and 2002 were reviewed. The analysis revealed that 203,021 (64%) of these reports did not contain useful event location information. Of the remaining reports, 102,303 (89%) incidents occurred in hospitals, 6,153 (5%) incidents occurred in outpatient treatment facilities, 2,511 (2%) incidents occurred in ambulatory surgical facilities, and 3,157 (3%) incidents occurred at home. The majority of the incidents that occurred at home involved blood glucose meters (42%), defibrillators (10%), ventilators (8%), and wheelchairs (5%). Home incidents resulted in 108 fatalities and 776 injuries. The majority of the fatalities were associated with defibrillators (32%), ventilators (19%), oximeters (8%), and hemodialysis devices (6%). Seven of the 21 fatal home ventilator-related incidents were attributed to low, delayed, or non-sounding alarms. Hospital incidents comprised 102,303 records, with 2,046 incidents resulting in fatalities. A large share of the fatal hospital incidents were related to defibrillators (11%), catheters (11%), heart valves (10%), pacemakers (5%), and ventilators (4%). Six fatal hospital ventilator-related incidents were attributed in part to delayed, silenced, or non-sounding alarms.

Complications Associated With Global Endometrial Ablation

In Brief OBJECTIVE To investigate the number and type of complications associated with global endometrial ablation using public-access governmental databanks. METHODS MEDLINE (PubMed) and the US Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) databases were searched for entries for the four US Food and Drug Administration–approved global endometrial ablation devices. RESULTS Traditional MEDLINE and bibliography searches yielded reports of two cases of hemorrhage, one case of pelvic inflammatory disease, 20 cases of endometritis, two cases of first-degree skin burns, nine cases of hematometra, and 16 cases of vaginitis and/or cystitis. A search of the US Food and Drug Administration MAUDE database yielded reports of 85 complications in 62 patients. These included major complications: eight cases of thermal bowel injury, 30 cases of uterine perforation, 12 cases in which emergent laparotomy was required, and three intensive care unit admissions. One patient developed necrotizing fasciitis and eventually underwent vulvectomy, ureterocutaneous ostomy, and bilateral below-the-knee amputations. One of the patients with thermal injury to the bowel died. CONCLUSION Use of the US Food and Drug Administration MAUDE database is helpful in identifying serious complications associated with global endometrial ablation not yet reported in the medical literature. Use of a public-access governmental database uncovered serious complications associated with global endometrial ablation devices.

Complications associated with global endometrial ablation: the utility of the MAUDE database

Objective To investigate the number and type of complications associated with global endometrial ablation using public-access governmental databanks. Methods MEDLINE (PubMed) and the US Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) databases were searched for entries for the four US Food and Drug Administration–approved global endometrial ablation devices. Results Traditional MEDLINE and bibliography searches yielded reports of two cases of hemorrhage, one case of pelvic inflammatory disease, 20 cases of endometritis, two cases of first-degree skin burns, nine cases of hematometra, and 16 cases of vaginitis and/or cystitis. A search of the US Food and Drug Administration MAUDE database yielded reports of 85 complications in 62 patients. These included major complications: eight cases of thermal bowel injury, 30 cases of uterine perforation, 12 cases in which emergent laparotomy was required, and three intensive care unit admissions. One patient developed necrotizing fasciitis and eventually underwent vulvectomy, ureterocutaneous ostomy, and bilateral below-the-knee amputations. One of the patients with thermal injury to the bowel died. Conclusion Use of the US Food and Drug Administration MAUDE database is helpful in identifying serious complications associated with global endometrial ablation not yet reported in the medical literature.

Intra-articular hyaluronans: A review of product-specific safety profiles

Background and Objectives: Intra-articular (IA) hyaluronans (HAs) are indicated for pain relief of osteoarthritis (OA) of the knee. Hyalgan (sodium hyaluronate), Supartz (sodium hyaluronate), and Synvisc (hylan G-F 20) are Food and Drug Administration-approved HA products. They are derived from rooster combs; Hyalgan and Supartz are naturally derived (unmodified); Synvisc is chemically modified to increase its molecular weight. This article reviews and updates the safety data for IA HAs used for the treatment of knee OA. Methods: References were taken from Medline through July 2002; respective product information services and information from the searchable United States Food and Drug Administration Manufacturer and User Facility Device Experience Database also were used. Results: All products demonstrated favorable safety profiles in clinical trials and practice compared to other standard therapies for management of OA knee pain. The most common adverse event associated with HAs is mild injection site pain and swelling. Each product has had rare reports of pseudogout and anaphylactoid reactions. Product-specific adverse events, severe acute inflammatory reactions (pseudoseptic knee), in patients receiving Synvisc have been reported. One such patient developed antibodies to chicken proteins and hylan, suggesting an immunologic basis for the severe acute inflammatory reaction. Data from an animal study support a possible immunogenic difference between Synvisc and Hyalgan. Conclusions and Relevance: Overall, HA therapy is a safe treatment for OA knee pain, although there may be interproduct variability in safety profiles. Semin Arthritis Rheum 32:296-309. Copyright 2003, Elsevier Inc. All rights reserved.

Overview of the Fourth International Conference on Harmonization

This overview of the Fourth International Conference on Harmonization (ICH 4), held in Brussels, Belgium, 16-18 July 1997, summarizes results and provides information regarding the nonclinical workshop and issued nonclinical testing guidelines [Draft Final (Step 4) Guidelines recommended for adoption to the regulatory bodies of the EU, Japan, and the USA]. ICH 4 completed the initial harmonization targets for the three ICH Regions [European Commission-European Union (EU) and European Federation of Pharmaceutical Industries' Association (EFPIA); Ministry of Health and Welfare (MHW) Japan and Japan Pharmaceutical Manufacturers Association (JPMA); and the U.S. Food and Drug Administration (FDA) and Pharmaceutical Research and Manufacturers of America (PhRMA)] and the International Federation of Pharmaceutical Manufacturers Associations (IFPMA). Proceedings will be available in book form. Earlier conferences, guidelines, and proceedings are available on CD-ROM and in print and diskette form from the ICH Secretariat, c/o IFPMA, 3 rue de St.-Jean, P.O. Box 9, 1211 Geneva 18, Switzerland; Tel +41 (22) 340 12 00; Fax +41 (22) 345 82 75. Similar information is obtainable from the ICH Home Page (http://www.ifpma.org/ich1.html) and the Pharm Web home page (http://www.pharmweb.net).

Direct-to-Consumer Advertising: Today's Issues and Tomorrow's Outlook

An extensive review of pharmacy and marketing literature shows that direct-to-consumer advertising (DTCA) strategies have changed significantly since the first advertisements were presented in the early 1980s. The future of DTCA, however, is still uncertain as the impact of this new marketing tactic on current health care practice is not yet fully understood. Physicians and pharmacists need to be aware of and respond to the knowledgeable patient, while the Food and Drug Administration (FDA) and pharmaceutical manufacturers must make cognizant decisions about the amount and the type of information that will be advertised directly to consumers. Finally, patients must understand the potential shortcomings of the information presented in prescription drug advertisements. This article will review the definition of DTCA, provide current examples of campaigns and their impact on health care communication, and predict changes that may occur as a result of FDA reconsideration of drug advertising regulations.