Center for Devices and Radiological Health 2003
Manufacturer of Anesthesia Device Receives Warning
On April 18, 2003, the FDA’s Cincinnati District Office issued a Warning Letter to Cardinal Medical Specialties, Inc., Louisville, Kentucky. The firm is a manufacturer of a Class II portable anesthesia device. The device is used to administer general inhalation anesthesia using mixtures of oxygen, air, and volatile anesthetics. It can also be used to provide breathing gas and either spontaneous or controlled ventilation of the patient's lungs. An FDA inspection of Cardinal Medical Specialties, Inc., was conducted on March 3 - May 3, 2003. The inspection disclosed significant deviations from the Quality System (QS) Regulation for devices. These deviations included:
- Failure to establish and maintain procedures for finished device acceptance;
- Failure to document finished device acceptance activities;
- Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met;
- Failure to establish and maintain a design history file for each type of device;
- Failure to maintain a device master record; and
- Failure to maintain device history records and to have procedures to ensure that device history records are maintained to demonstrate that the device is manufactured in accordance with the device master record.
Class I Recall - Manual Resuscitator Recalled
Patient Injuries Result in Class I Recall
The FDA reported that on November 15, 2002, Portex Inc., Keene, New Hampshire, initiated a Class 1 recall of the product, Portex 1st Response Adult Manual Resuscitator Sims. This manual ventilator is used as a breathing-assist device intended to provide respiratory support to patients suffering breathing distress and whose body weight is 55 pounds (25 kg) or more. The firm initiated the recall by telephone on November 15, 2002, and November 18, 2002, and by letter dated November 19, 2002.
The recall was initiated because the preset positive expiratory end pressure (PEEP) valve was set to its maximum pressure of 20 cm H20 and could result in patient injury if the product label was not read and product not adjusted at the time of use. There were at least two patient injuries requiring patients to be placed on a ventilator due to the inadvertent delivery of excess PEEP during resuscitation attempts.
FDA classified this recall as a Class I because there is a reasonable probability that use of the product will cause serious adverse health consequences.
Firm Stops Manufacturing Following FDA Warning Letter
On April 30, 2003, the FDA’s Atlanta District Office issued a Warning Letter to the Acting CEO and Vice President of Marketing, Systems 02, Inc., located in Roswell, Georgia. The firm was manufacturing and distributing System 02 and Rejuv 02 portable oxygen generators. The FDA’s inspection of the firm from December 10-17, 2002, revealed numerous and significant violations of the Quality System Regulation.
In addition, the firm did not have a cleared 510(k) for the device as labeled. Testing of the device revealed that it did not produce the level of oxygen required. The firm agreed to initiate a recall of all devices distributed and to stop any further distribution. FDA worked with the firm to find a suitable disposition of their remaining devices.
Warning Letter Issued for QS Regulation Violations
On April 7, 2003, the FDA’s Center for Devices and Radiological Health issued a Warning Letter to SagaTech Electronics, Inc, located in Calgary, Alberta, Canada. FDA also placed the firm on Detention without Physical Examination. The firm manufactures sleep assessment devices. The FDA inspection revealed numerous quality system violations including the following:
- Failure to establish and maintain adequate procedures to control the design of the device in order to ensure that specified requirements are met.
- Failure to establish and maintain adequate procedures for implementing corrective and preventive action.
- Failure to establish and maintain adequate procedures to ensure that any complaint that represents an event that must be reported to FDA shall be promptly reviewed, evaluated, and investigated by a designated individual(s) and shall be maintained in a separate portion of the complaint files or otherwise clearly identified.
- Failure to establish and maintain procedures for changes to a specification, method, process, or procedure to ensure that the device conforms to its specifications.
- Failure to establish procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system.
- Failure to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures.
FDA Fines Ophthalmologist $1.1 Million for Clinical Study Violations
Clinical Investigator Used Unapproved LASIK Device Outside the Parameters of Clinical Protocol
A Lafayette, Louisiana ophthalmologist and the eye care center he owns have agreed to pay the federal government a total of $1.1 million in civil money penalties for violating federal laws related to the conduct of clinical studies. The violations involved studies of a laser system built by the ophthalmologist for LASIK treatment of nearsightedness.
In a settlement agreement reached with FDA, Leon C. LaHaye, M.D., will pay $150,000 and his LaHaye Center for Advanced Eye Care of Lafayette will pay $950,000 for clinical study violations on at least 175 occasions. LaHaye was also disqualified by FDA in June 2002, from conducting further clinical studies.
“This penalty sends a clear message to study sponsors: FDA will not tolerate misconduct of clinical studies. This puts participants at risk and is a serious violation of the law,” said FDA Commissioner Mark B. McClellan, M.D., Ph.D.
FDA regulations establish strict conditions under which clinical studies of medical devices may occur. For example, studies of high risk devices such as ophthalmic lasers must be conducted according to an investigational plan reviewed and approved by FDA and an investigator must obtain informed consent from each participant. In addition, the device cannot be used on patients before the study begins.
Charges against Dr. LaHaye included:
- Treating more subjects than allowed under the study plan that was approved by FDA;
- Ignoring parameters of the study by treating nearsightedness beyond the permitted range and by treating astigmatism and both eyes of some patients;
- Failing to submit complete, accurate and timely reports to the FDA about the ongoing studies; and
- Misrepresenting to FDA that he was using an FDA-approved laser to treat patients when, in fact, the procedures were performed with an unapproved, experimental laser.
The settlement agreement was signed before an administrative law judge of the FDA.
Clinical Investigator Found Implanting Unapproved Devices
FDA Inspection Finds Clinical Investigator Using Unapproved Device
On March 17, 2003, the FDA’s Center for Devices and Radiological Health issued a Warning Letter to Edward B. Diethrich, M..D., Arizona Heart Institute, Interventional Research Department, Phoenix, Arizona. The Warning Letter informed Dr. Diethrich of violative conditions found during an FDA inspection at the clinical site. The Warning Letter requested immediate corrective actions.
From October 22 through November 01, 2002, an investigator from the FDA’s Los Angeles District Office conducted an inspection of the clinical facility. The purpose of the inspection was to determine whether Dr. Diethrich’s activities as a sponsor and principal investigator of investigational studies with “significant risk” devices complied with applicable FDA regulations. The inspection revealed research and the use of “significant risk” study devices.
The inspection was conducted under a Bioresearch Monitoring Program designed, in part, to ensure that data and information contained in applications for Investigational Device Exemptions (IDEs) are scientifically valid and accurate. Another objective of this program is to ensure that human subjects are protected from undue hazard or risk during the course of the scientific investigations.
The inspection at Arizona Heart Institute (AHI) covered four protocols having Investigational Device Exemptions (IDEs). The products used in these studies are devices as that term is defined in Section 201(h) of the Federal Food, Drug, and Cosmetic Act.
During the inspection the FDA investigator documented that Dr. Diethrich was treating subjects with an unapproved, “significant risk” medical device. The Warning Letter noted that the device had not been approved by FDA for this or any other use, nor had it been approved for investigational use.
In Dr. Diethrich’s written response to the inspection, he stated that the devices did not need an approved IDE because they were custom devices.
The custom device exemption applies to devices that meet a narrow and specific set of statutory requirements. The devices that Dr. Diethrich implanted did not meet these requirements: they were simply ordered individually from existing pre-manufactured stock.
The Warning Letter advised Dr. Diethrich as follows:
“Continued implantation of these devices will be considered by FDA to be knowingly violating the Food, Drug, and Cosmetic Act. Please submit a written response to this letter, identifying all human subjects who received the [redacted] or any other unapproved device, by name, address and date of implantation. To protect the rights and welfare of the human subjects you implanted, you must develop a corrective action plan that includes, at a minimum, notification of each recipient by certified mail that they were implanted with an unapproved device, who to contact in the event of an emergency, and where to report adverse events. Your corrective action plan should be submitted to this office for approval prior to implementation. Copies of all letters sent to implant recipients should also be submitted to this office.”
”Within 15 days, you must respond to this letter in writing. You should be aware that FDA considers your actions to be serious violations of the law and your failure to respond may result in FDA taking regulatory action without further notice to you. These actions include, but are not limited to, investigator disqualification, seizing product inventory, obtaining an injunction to prevent further violations of the law, assessment of civil money penalties, and criminal prosecution.”
The Division of Bioresearch Monitoring participated in a follow-up inspection of Dr. Diethrich at AHI in November 2003. Dr. Diethrich received the above discussed Warning Letter on March 17, 2003 for implanting 68 patients with an unapproved device. The inspection concentrated on the corrective action plan (CAP) outlined by Dr. Diethrich in his response to the Warning Letter and the other requirements in the Warning Letter. The inspection revealed that Dr. Diethrich and his staff contacted all living patients who received the unapproved device by certified mail. Dr. Diethrich’s Excel sheets documented that the tracking log for the certified letter to patients, the follow-up testing post implant log sheet, and the adverse events log sheet were up to date, complete and accurate. The inspection was classified as no action indicated (NAI) and demonstrated the impact of an FDA presence on Human Subject Protection in device research.
Warning Letter Issued to a Clinical Investigator
IRB Suspends Clinical Investigator’s Participation in Study of Pediatric Patients
The Division of Bioresearch Monitoring issued a Warning Letter to Dr. David Skaggs a clinical investigator studying an implantable prosthetic device for children. Violations noted during the inspection included the following: failure to provide pediatric study subjects with adequate informed consent in that two subjects spoke a foreign language and were not provided an informed consent prior to surgery in a language understandable to them or their representatives; failure to obtain informed consents from additional pediatric subjects prior to surgery; failure to ensure that the investigation was conducted according to the signed agreement with the sponsor and investigational plan; and failure to maintain accurate study records.
As a result of these findings, the local Institutional Review Board (IRB) suspended Dr. Skaggs participation in this study. The Division of Bioresearch Monitoring asked Dr. Skaggs to respond within 15 working days of receipt of the Warning Letter with the corrective actions he had taken or plans to take to avoid a repeat of the deviations noted in future studies.
Warning Letter Advises Investigator to Immediately Cease Investigation
FDA Inspection Discloses Investigator Conducting Study Without FDA or IRB Approval
On June 25, 2003, the FDA’s Center for Devices and Radiological Health (CDRH) issued a Warning Letter to Dr. Gerald M. Burma, Parma Community General Hospital, Parma, Ohio. An FDA inspection of the clinical site on November 13, 2002, through January 17, 2003, revealed violations of the requirements of Title 21 Code of Federal Regulations (CFR) Part 50 - Protection of Human Subjects and Part 812 - Investigational Device Exemptions. The violations included the following:
- Failure to obtain FDA approval prior to beginning this study;
- Failure to follow the conditions of approval imposed by the Institutional Review Board (IRB) and failure to report adverse events to the IRB;
- Failure to obtain adequate informed consent; and
- Failure to prepare and maintain accurate, complete, and current records relating to the conduct of the investigation.
The Warning Letter advised Dr. Burma that he should immediately cease conducting these investigations on human subjects. In addition, the Warning Letter advised Dr. Burma that conducting such clinical investigations without an approved Investigational Device Exemption (IDE) application is prohibited under Section 301(q)(1) of the Federal Food, Drug, and Cosmetic Act. Therefore, Dr. Burma must obtain FDA approval before continuing his research.
Intra Aortic Balloon Insertion Kit Recalled
The FDA’s New Jersey District Office was alerted by Datascope, Cardiac Division, Fairfield, New Jersey, of a recall of its 10.5 Fr. Percor STAT DL Intra Aortic Balloon Insertion Kit, lot BRV exp. March 5, 2003. The manufacturer, Datascope, initiated the recall by letter on March 28 and 31, 2003. The kits contained an Introducer Sheath. The introducer sheath, after it is dilated by the introducer dilator, is intended to assist the percutaneous insertion of the 10.5 Fr. Intra-Aortic Balloon catheter into the vasculature.
The firm had tested another similar “not distributed” Introducer Sheath lot and found that the kit failed the final water leak test. Upon learning of this failure, the firm conducted a water leak test on the “now recalled lot” and found that this lot also failed the test. Recall letters were sent to hospitals. The New Jersey District monitored the recall to completion.
The FDA reported that on October 14, 2002, Access Cardiosystems, Inc., Concord, Massachusetts, initiated a recall of their Portable Automated External Defibrillators [AED], Model No. 9100-0100: a) AccessAED; and b) AccessALS by mail. The volume of product was 227 devices with distribution to Arizona, New York, Maryland, Nevada, Oregon, Texas, Washington, and Wisconsin. The product was also distributed internationally. The reason for the recall was that the Portable External Defibrillator “may fail self test and fail to function.”
Warning Letter Issued for Violations of the Quality System and Medical Device Reporting Regulations
Manufacturer of Device for Heart Rate and Cardiac Output Fails to Report Serious Injury
On March 13, 2003, the FDA’s Florida District Office issued a Warning Letter to CardioCommand, Inc., Tampa, Florida, for violations of the Quality System (QS) and Medical Device Reporting (MDR) Regulations. These violations were observed during an inspection on March 5 - 10, 2003. The firm is a manufacturer of devices for pacing and controlling of heart rate and cardiac output. The QS violations included the following:
- Failure to establish procedures for quality audits and to conduct such audits to assure that their quality system is in compliance;
- Failure to establish and maintain procedures for identifying the actions needed to correct and prevent recurrence of non conforming product and other quality problems;
- Failure to verify or validate the corrective or preventive action to ensure that such action is effective and does not adversely affect the finished device;
- Failure to validate and approve a process whose results cannot be fully verified by subsequent inspection and test, and to document the validation activities and results;
- Failure to establish and maintain quality system requirements;
- Failure to document and review periodic inspections of environmental control systems;
- Failure to establish and maintain procedures for the identification, documentation, validation, verification, review and approval of design changes before their implementation; and
- Failure to have a formally designated unit maintain a record of an investigation.
The firm failed to submit a serious injury report to the FDA as required by the MDR regulations and failed to submit a premarket approval (PMA) supplement for cardiac catheters.
Medical Device Reprocessor Signs Consent Decree
Firm Fails to Correct Problems Despite Warnings from FDA
On August 7, 2003, FDA announced that Adven Medical, Inc., of Lubbock, Texas, and its president, Mark W. Aldana, had signed a consent decree of permanent injunction in which the firm agreed to stop reprocessing and distributing medical devices until Adven Medical corrects its manufacturing problems. Adven Medical was cited by the FDA for failing to comply with the Quality System regulation when it reprocessed single-use medical devices.
The firm reprocessed different kinds of single-use medical devices, such as catheters, biopsy forceps, sutures, and blood pressure cuffs. Some of these devices were used on patients. Others were opened but unused or were past their expiration dates. Many hospitals and medical care facilities use reprocessed single-use devices because it is less expensive to clean, and disinfect or sterilize them compared to purchasing new products.
FDA found numerous violations of the good manufacturing practice requirements of the Quality System (QS) Regulation during inspections of the firm. Adven Medical violated FDA’s QS Regulation by failing to: (1) validate its cleaning, disinfecting, and sterilization processes; (2) adequately establish and maintain procedures to validate medical device designs; (3) establish and maintain procedures to prevent and correct manufacturing problems; and (4) use adequate criteria to ensure that finished devices meet their design specifications.
Adven Medical was re-inspected in August and September 2003. The inspection revealed that the firm failed to make the necessary corrections to meet the requirements of the QS regulations. Adven Medical decided to permanently close its doors on October 15, 2003.
Adven Medical’s history of non-compliance dates back to June 1999 when, under a partnership with FDA, the Texas Department of Health inspected Adven Medical 's manufacturing facility. Many of the problems observed in that inspection recurred, along with new problems, in later FDA inspections. Adven Medical failed to correct these problems.
The consent for permanent injunction was filed in the United States District Court for the Northern District of Texas, Lubbock Division. Adven Medical will not be allowed to resume reprocessing and distributing medical devices until FDA is satisfied that it has corrected its manufacturing problems.
Firm Found Selling an Unapproved Dental Water Purification System
On February 5, 2003, the FDA’s Los Angeles District Office issued a Warning Letter to Master Industries, LLC, Orange, California, for the illegal manufacturing and selling of a medical device product, the Master Industries System 2000 Water Purification System, also known as the UV Module 10 003. The device is intended to reduce bacterial levels in dental operatory water lines.
The firm was informed that their product is considered a device as defined in section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act), and that they had not notified the FDA of the device per section 510(k) of the Act, nor did they have an approved premarket approval application in effect under section 515(a) nor an approved application for an investigational device exemption under 520(g) of the Act.
In addition, the firm was notified that there were significant deviations from the Quality System Regulation for devices. These deviations included the following:
- Failure to establish and maintain a quality system that is appropriate for the specific medical device designed and manufactured;
- Failure to establish a quality policy and objectives. Specifically, management with executive responsibility had not ensured that a quality policy was established that satisfied the requirements of the Quality System Regulation;
- Failure to appoint a management representative to ensure that quality system requirements are effectively established and maintained, and to report to management on the performance of the quality system;
- Failure to conduct quality audits at sufficient regular intervals, as prescribed by internal procedures to verify that the quality system is effective in fulfilling quality system objectives.;
- Failure to establish procedures to control the design of the device;
- Failure to establish procedures for implementing corrective and preventive actions;
- Failure to establish process control procedures that describe any process controls necessary to ensure conformance to specifications; and
- Failure to maintain a Device Master Record which includes device specifications, production process specifications, quality assurance procedures, packaging and labeling specifications, and installation, maintenance, and servicing procedures.
Firm Voluntarily Destroys Gauze Bandages
On June 16, 2003, the FDA’s Chicago District Office witnessed the voluntary destruction of various gauze bandages at Textus Industries, Inc., Peoria, Illinois. These products were manufactured in China at a facility partly owned by this firm and a portion of the products were sterilized domestically. Previous FDA inspections of the firm disclosed several Quality System Regulation deficiencies, including a failed sterile package integrity testing of a product sample that resulted in the issuance of a Warning Letter to the firm.
Warning Letter Issued for Failure to Report Injuries
Despite Reports of Injuries Firm Fails to File Medical Device Report
On March 4, 2003, the FDA’s Detroit District Office issued a Warning Letter to Innovative Products Unlimited, Inc., Appleton, Wisconsin. The Warning Letter concerned violations of the Quality System (QS) and Medical Device Reporting regulations documented during an FDA inspection of the firm’s manufacturing plant in Niles, Minnesota, on May 28 - June 2, 2002.
The firm makes a line of gurneys and patient shower chairs from plastic tubing materials with casters. The products are used to facilitate the transport and support of disabled and elderly patients during bathing. There were several complaints of injuries resulting from broken or separated parts of the devices that resulted in patients falling. No Medical Device Reports had ever been filed by the firm. The firm also failed to comply with the design control requirements on some more recently developed models and products, and also failed to comply with most of the management controls, auditing, and records requirements of the QS Regulation.
FDA Inspection Documents Significant Violations
The FDA’s Florida District Office issued a Warning Letter on April 23, 2003, to Alpha Industries, Inc., Clearwater, Florida, for violations of the Quality System (QS) and the Medical Device Reporting (MDR) Regulation. An FDA inspection conducted on March 17 to April 2, 2003, disclosed these violations. The firm is a manufacturer of umbilical cord clamps, tubing clamps, hemostats, and forceps. The QS violations included the following:
- Failure to establish and maintain procedures for implementing corrective and preventive actions (CAPA) and to document CAPA activities;
- Failure to establish, document and implement quality system QS procedures and instructions;
- Failure to establish and maintain requirements, including quality requirements that must be met by suppliers and contractors;
- Failure to establish procedures to identify training needs and ensure all personnel have been trained to perform their assigned responsibilities; and
- Failure to establish and maintain written Medical Device Reporting procedures.
FDA Finds Problems at a Firm Following a Recall
On April 21, 2003, the FDA’s New York District Office issued a Warning Letter to Tyco International, Inc., Portsmouth, New Hampshire. The FDA issued the Warning Letter for violations of the Quality System Regulation found at Tyco Healthcare/Kendall Division, Argyle, New York. The firm had conducted a recall of their 3.7 Fr umbilical vessel catheters for neonates due to complaints that the lumen of the catheter may not accommodate the designated sensor promoted with the product. Deficiencies with design changes, final acceptance activities, and production and process controls were documented during the follow up inspection.
An FDA inspection of the firm on January 5, to February 8, 2003, revealed the following violations:
- Failure to establish and maintain an adequate design change procedure; and
- Failure to adequately establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria.
Fiber Optic Cable Firm Receives Warning
On April 9, 2003, the FDA’s New York District Office issued a Warning Letter to Designs for Vision, Inc., of Ronkonkoma, New York, a manufacturer of Class II medical devices. The firm manufactures the "DayLite XeNon Light Source," which is used with a fiber optic cable and headset to provide illumination during surgery and other procedures. During an FDA inspection of this establishment on March 24 - 28, 2003, the FDA investigator observed significant non conformance with the Quality System Regulation for medical devices. The following violations were detailed in the Warning Letter:
- Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit;
- Failure to develop, maintain, and implement written medical device reporting procedures;
- Failure to establish procedures for quality audits and to conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system;
- Failure of management with executive responsibility to establish its policy and objectives for, and commitment to quality;
- Failure to establish and maintain procedures to control product that does not conform to specified requirements;
- Failure to establish and maintain the requirements, including quality requirements, that must be met by suppliers;
- Failure to establish and maintain procedures for finished device acceptance to ensure that each finished device meets acceptance criteria;
- Failure to review and approve changes to documents;
- Failure to document personnel training; and,
- Failure to establish and maintain procedures to ensure that equipment is routinely calibrated.
The Warning Letter advised that “…management should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action being initiated by the FDA without further notice.”
FTC and FDA Work Together Against Fraudulent Products on the Internet
The FDA, together with the Federal Trade Commission (FTC), have formed a coordinated, ongoing and comprehensive law enforcement and consumer education effort with Health Canada, and various state Attorneys General. This effort, called "Operation Cure.All," began in 1997 to crack down on unscrupulous marketers who use the Internet to prey on the sickest and most vulnerable consumers.
As a result of these efforts, FTC announced on January 27, 2003, that the FTC had charged a Switzerland-based company and its U.S. counterpart with making numerous unsubstantiated efficacy claims for a variety of devices that they were selling on the Internet. In its complaint filed in federal court, the FTC alleged that the defendants advertised that their products and programs could cure advanced and terminal cancers, AIDS, and other serious diseases. The FTC's complaint named Dr. Clark Research Association (DCRA), a California corporation that uses a San Diego, California, address; Dr. Clark Behandlungzentrum GMbH, a company based in Munchenbuchsee, Switzerland, and doing business as Dr. Clark Zentrum (DCZ), and their owner, David P. Amrein.
The FDA Commissioner Mark McClellan, M.D., Ph.D., stated, "The FDA takes a dim view of devices that make phony claims to cure or treat serious disease or illness. Besides being a waste of money, such products can prevent the user from obtaining needed medical treatment. FDA will continue to monitor the Internet and other sources for devices that make false medical claims and work with the FTC to get them off the market."
The products at issue are:
- The "Zapper," (sold as the "Super-Zapper Deluxe") a device that purportedly kills disease causing parasites in the body with electricity;
- The "Syncrometer," a device that purportedly can diagnose diseases;
- "Dr. Clark's New 21 Day Program for Advanced Cancers," a regimen that includes dietary supplements. It purportedly cures advanced cases of cancer, and, when used with the "Super-Zapper Deluxe," renders surgery and chemotherapy unnecessary; and
- The "Complete Herbal Parasite Program" - also called the Herbal Parasite Cleanse.
Class I Recall of ProbeTec ET Instrument
On July 21, 2003, the FDA's Center for Devices and Radiological Health posted a Class I recall notice for the ProbeTec ET Instrument, an in-vitro diagnostic medical device used for the detection of Chlamydia and Gonorrhea in symptomatic and asymptomatic patients. The recalling firm was Becton Dickinson of Sparks, Maryland. A component of the in-vitro diagnostic device was incorrectly installed causing false positive and false negative results. Continued use of the defective instrument could result in a moderate to high risk of serious adverse health consequences, including death.
Scanning Microscope is Unapproved Device
On March 28, 2003, the FDA’s Center for Devices and Radiological Health (CDRH), Office of In Vitro Diagnostic Device Evaluation and Safety, issued a Warning Letter to Mr. Carl Hull, Chief Executive Officer, Applied Imaging Corporation, Santa Clara, California. The Warning Letter advised Mr. Hull that the FDA had reviewed a folder of information entitled “It’s Time,” regarding the firm’s ariol SL-50 automated image analysis system (ariol SL-50). FDA noted that CDRH also reviewed the firm’s Internet site, http://www.aicorp.com.
The ariol ST-50 is a medical device as defined by Section 201 (h) of the Federal Food, Drug, and Cosmetic Act. Specifically, the device is an automated scanning microscope and image analysis system. There is no application on file with FDA for the ariol SL-50 device.
The Warning Letter stated that the “It’s Time” folder, the brochures found within the folder, and information on Applied Imaging’s website created intended uses for the ariol SL-50 device which have not been evaluated by FDA. The firm’s folder states that the ariol SL-50 can be used for “occult tumor cell detection in bone marrow.” A brochure in the folder, entitled “Ariol Imaging Module Panel - 2002,” states that the system’s Kisight’ module provides “[r]apid image analysis for efficient quantification and scoring of IHC stained tissue for nuclear markers.”
The firm’s folder, brochures, and website state that the ariol SL-50 is not for use in diagnostic procedures and is for “research use only.” “Research use only” is a term used to describe products in the initial research phase of development that are not represented as effective in vitro diagnostic products. It is clear from the medical and diagnostic claims made for the ariol SL-50 in the promotional materials that this product is not in the research phase of development.
The Warning Letter stated that the ariol SL-50 device was adulterated because it is a class III device which does not have an approved application for premarket approval in effect, or an approved application for investigational device exemption. This device is also misbranded because a notice or other information respecting the device was not provided to the FDA.
The Warning Letter advised that the firm “…should take prompt action to correct these violations. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties.”
Congress passed the Mammography Quality Standards Act of 1992 (MQSA). After passage of the MQSA, FDA received authority from the Department of Health and Human Services to implement MQSA.
Facilities that fail accreditation and are not MQSA certified must stop performing mammography. However, once a facility has corrected the problems that caused the failure, it may apply for reinstatement to reenter the accreditation process. Facility certification can now be extended to include FDA-approved Full Field Digital Mammography (FFDM) units.
FDA qualifies MQSA inspectors who meet specific qualifications and who must maintain this qualification by meeting continuing education and experience requirements. Inspectors receive specialized training in radiation physics, physics related to mammography equipment, and inspecting mammography facilities’ compliance with MQSA regulations. All inspectors must pass a series of hands-on tests prior to independently performing inspections.
FDA has classified each adverse inspection into one of three category levels:
- A Level 1 observation indicates a failure to meet a key MQSA requirement that may compromise the quality of mammography performed at the facility.
- A Level 2 observation indicates that the facility meets all key MQSA requirements but fails to meet a significant mammography quality item.
- A Level 3 observation indicates that the facility meets all major MQSA requirements with only minor problems.
Adverse inspectional observations are placed into a category level based on FDA’s assessment of how the observation may affect the quality of mammography. The category level is also used to determine how the facility should respond to the observation. Identical observations found during two consecutive inspections are identified as repeats.
Warning Letters Issued for Violations of the MQSA
- On June 19, 2003, the FDA’s Florida District Office issued a Warning Letter to Drew Medical, Inc., Orlando, Florida, due to violations documented during a State inspection on April 23, 2003, of this mammography facility. The facility failed to administer a processor performance test on each day that clinical films were processed; failed to produce documents verifying that a radiologic technologist taught or had completed at least 15 continuous education units; and failed to maintain the optical density of the film at the center of an image of a standard FDA accepted phantom of at least 1.20.
- On July 14, 2003, the FDA’s Baltimore District Office issued a Warning Letter to Breast Imaging at Mercy Medical Center, Baltimore, Maryland. An inspection by the State of Maryland on behalf of the FDA on June 24, 2003, revealed deficiencies related to the MQSA. The findings included two repeat Level 2 findings as follows: failure to document weekly phantom quality control testing, and failure to specify procedures for collecting and resolving consumer complaints.
- On August 8, 2003, the FDA’s Detroit District Office issued a Warning Letter to Winona Memorial Hospital, Indianapolis, Indiana. The Warning Letter was based on an inspection by the State of Indiana conducted on July 10, 2003, on behalf of the FDA. The inspection revealed that the facility had repeat Level 2 findings regarding failure to provide verification that two technologists met the continuing education and experience requirements of the MQSA.
In addition, the Warning Letter stated that the firm should also address the following Level 2 and Repeat Level 3 findings that were listed on the inspection report: failure to produce documentation that the interpreting physician met the continuing experience requirement of having interpreted or multi-read 960 mammograms in the previous 24 month period. The fixer retention quality control testing for the mammography film processor was inadequate because the test was not conducted at the required frequency of at least quarterly.
- On April 28, 2003, the FDA’s Detroit District Office issued a Warning Letter to Northland Radiology, Detroit, Michigan, a mammography facility. A representative of the State of Michigan, acting on behalf of the FDA, conducted an inspection of the facility on April 11, 2003. The inspection revealed serious deficiencies in the quality of the mammography services offered at the facility in that the phantom image score was less than two masses after subtracting for any mass like image artifacts.
- On April 28, 2003, the FDA’s Cincinnati District Office issued a Warning Letter to Robinson Memorial, Ravenna, Ohio. An inspection by a representative of the State of Ohio, on behalf of FDA, documented significant MQSA Level 1 and Level 2 noncompliances including, failure to issue timely lay summary letters to patients with “Suspicious” and “Highly suggestive for malignancy” results, and failure to report overall final assessment of findings on several mammographic examinations.
- On April 8, 2003, the FDA’s Detroit District Office issued a Warning Letter to the Methodist Hospital Breast Center, Indianapolis, Indiana, based on an inspection on March 26, 2003. The inspection was performed by the State of Indiana on behalf of the FDA.
- The inspection documented Level 1 deficiencies as follows: the facility failed to produce documentation to show that the interpreting physician met the initial requirement of being certified in an appropriate specialty area by an FDA approved board or having received 3 months of initial training in the interpretation of mammograms; and the facility failed to produce documentation to show that the interpreting physician met the initial requirement of being certified in a appropriate specialty area by an FDA approved board or having 3 months of initial training in the interpretation of mammograms.
- The FDA’s Minneapolis District Office issued a Warning Letter on February 20, 2003, to Ortonville Area Health Services, Ortonville, Minnesota. An inspection on January 15, 2003, conducted by a representative from the state of Minnesota, on behalf of FDA, disclosed that ten of ten random reports reviewed did not contain an acceptable mammography assessment category. The clinic was cited for repeat Level 2 violations of the MQSA.
- The FDA’s Minneapolis District Office issued a Warning Letter on August 19, 2003, to Avera Gregory Healthcare Center in Gregory, South Dakota, for violations of the MQSA. An inspection was conducted on July 15, 2003, by the State of South Dakota, under contract with FDA. The inspection revealed a Level 1 non compliance in that the radiologic technologist did not meet the initial requirement of holding either a valid state license or valid certificate from an FDA approved body.
Violations Found With Obstetrics and Gynecology Ultrasound Information and Reporting Systems
On April 14, 2003, the FDA’s Los Angeles District Office issued a Warning Letter for violations of the Quality System Regulation at Vision Chips, Inc., Aliso Viejo, California. The firm is a software device manufacturer of Obstetrics and Gynecology ultrasound information and reporting systems and an integrated image archiving system. The Warning Letter was based on an initial inspection of the firm on March 4 - 5, 2003. The inspection revealed numerous significant failures to comply with Quality System Regulation requirements involving management controls, design controls, and corrective and preventive actions. Although the firm had previously responded to the FDA-483 promising corrections, the responses were not deemed adequate to ensure correction of the violations.
Adhesion Prevention Solution Voluntarily Withdrawn from the Market
Firm Withdraws Device Following Reports of Adverse Events
On April 16, 2003, FDA posted a Notice on the Agency’s Website that GYNECARE Worldwide, a division of Ethicon, Inc., of Somerville, New Jersey, had notified FDA that they were voluntarily withdrawing “GYNECARE INTERGEL Adhesion Prevention Solution” from the global market and were urging customers to immediately stop using this device. The product had been distributed in the following countries; Austria, Canada, Egypt, England, France, Germany, Greece, Ireland, Israel, Italy, Japan, Kuwait, Netherlands, Portugal, Republic of Singapore, Saudi Arabia, Scotland, South Africa, Spain, Sweden, Switzerland, United Arab Emirates and the United States.
This product is intended to be used in open, conservative gynecological surgery as an adjunct to good surgical technique to reduce post-surgical adhesions. GYNECARE conducted a voluntary withdrawal to complete an assessment of information obtained during post-marketing experience with the device, including adverse events associated with off-label use in laparoscopy and non-conservative surgical procedures such as hysterectomy.
Post-market reports included late-onset post-operative pain and repeat surgeries following the onset of pain, non-infectious foreign body reactions, and tissue adherence. In some patients a residual material was observed during the repeat surgery. Post-operative pain could be suggestive of other serious complications and physicians should be aware of this in managing patients in the post-operative period.
GYNECARE withdrew the device from the market to conduct a full and thorough assessment of technical issues, surgical techniques and circumstances associated with the post-market events. GYNECARE requested that all GYNECARE INTERGEL product and samples be returned to GYNECARE.
Breast Pump Not Substantially Equivalent
On August 1, 2003, the FDA’s New England District Office issued a Warning Letter to The First Years, Inc., Avone, Massachusetts. On May 6, 2003, an investigator from the FDA’s New England District Office collected information that revealed a serious regulatory problem involving the product known as Natural Comfort TM breast pump, Catalog/Model No. 1075, which is made and marketed by the firm. The information disclosed that the Natural ComfortTM Breast Pump, was being shipped in interstate commerce without premarket notification. The Warning Letter advised the firm that the law requires that manufacturers of medical devices obtain marketing approval or clearance for their products from the FDA before they may offer them for sale. FDA records did not show that the firm obtained marketing clearance before offering the automatic suction release cycle breast pump for sale.
In addition, the Warning Letter noted that FDA had determined that the firm’s electronic control pump is significantly different from the manual suction release breast pump that was found to be substantially equivalent under Section 510(k), K964403. This change from manual suction release, as found on the cleared breast pump, to automatic suction release, requires the submission of a new premarket notification because it involves major modifications to the technology or performance of the device. Because the firm did not have marketing clearance from the FDA, marketing the modified product is a violation of the law.
Ophthalmic Surgical Sponge Firm Receives Warning
On February 3, 2003, the FDA’s New England District Office issued a Warning Letter to Ultracell Medical Technologies, North Stonington, Connecticut. The New England District conducted an inspection of the firm on December 17, 18, 23, and 31, 2002. The firm is a manufacturer of ophthalmic surgical sponges. The inspection revealed that these devices were adulterated because they were not in conformance with the Quality System Regulation for medical devices. The firm previously recalled numerous lots of product due to a sterility audit failure. The deviations documented during the inspection included the following:
- Failure to establish and maintain procedures for monitoring and controlling process parameters to ensure that specified requirements continue to be met;
- Failure to review and evaluate the process or perform revalidation when changes or process deviations occur; and
- Failure to document corrective and preventive actions, including investigations of causes of nonconformances, the actions needed to correct or prevent recurrence of nonconforming product and other quality problems, and the verifications or validation of corrective actions.
Warning Letter Issued for Transcend Hip System
On August 11, 2003, the FDA’s New Orleans District Office issued a Warning Letter to Wright Medical Technology, Inc., Arlington, Tennessee, in regard to the manufacture and distribution of a Transcend Hip System, a ceramic on ceramic Hip Articulation System. An inspection of the firm on April 28 - May 7, 2003, disclosed deviations from the Quality System Regulation.
The deviations included the distribution of the Transcend Hip System without completing process validation activities and adequately establishing and maintaining the quality requirements of the Liner. For example, the liner was manufactured in July 1999, prior to the completion of process validation by the contract manufacturer for processes such as pressing-green-machining, HIP-sintering, lapping, polishing, grinding, laser-engraving, and cleaning.
Inspection of Chinese Facility Discloses Regulatory Problems
On February 4, 2003, the FDA’s Center for Devices and Radiological Health, Office of Compliance, issued a Warning Letter to Merits Health Products, Co., Ltd. FDA investigators conducted an inspection of the facility on September 16 -19, 2002. This inspection revealed serious regulatory problems involving various models of Powered Wheelchairs and Electric Scooters sold under the brand names of Merits, Dalton, Rascal, Jazzy, and Jet, and the Q150 Pioneer Oxygen Concentrator, manufactured at Merits Health Products Co., Ltd.
The Warning Letter advised the firm that under United States law, the Federal Food, Drug, and Cosmetic Act (the Act), these products are considered devices because they are intended for use in diagnosing or treating a medical condition or to affect the structure or function of the body. The above-stated inspection revealed that these devices were not in conformance with the Quality System (QS) Regulation, as specified in Title 21, Code of Federal Regulations (CFR), Part 820. Significant deviations included, but were not limited to the following:
- Failure to establish and maintain adequate procedures for verifying the device design to confirm that the design output meets the design input requirements;
- Failure to validate computer software for its intended use according to an established protocol when computers or automated data processing systems are used as part of production or the quality system;
- Failure to establish and maintain adequate procedures to address and document the evaluation of nonconforming product, to include a determination of the need for an investigation of the nonconformance;
- Failure to document in the device history record the results of rework, including reevaluation, of nonconforming product after rework; and,
- Failure to establish and maintain adequate procedures for implementing corrective and preventive action for investigating the cause of nonconformities relating to the product, processes, and the quality system.
The Warning Letter advised the firm’s management that if they failed to take prompt action to correct these deviations, the FDA may take regulatory action without further notice. For example, products could be detained without physical examination upon entry into the United States, on the grounds that they appear to be adulterated under Section 501(h) of the Act. In addition, United States federal agencies are advised of the issuance of all Warning Letters about medical devices so that they may take this information into account when considering the award of contracts.
FDA Inspection Documents Numerous Violations of the QS
On August 18, 2003, the FDA’s Cincinnati District Office issued a Warning Letter to the President of Bioflex, Inc., Columbus, Ohio. An FDA inspection of the firm on July 14, 17, and 21, 2003, revealed that the firm manufactures electrical stimulation devices.
During the FDA inspection, major violations were documented regarding compliance with the Quality System Regulation. These deficiencies included failure to establish: (1) management controls; (2) a corrective and preventive action system; (3) design controls; (4) a Device Master Record; (4) complaint handling procedures; (5) calibration and maintenance procedures; and (6) Medical Device Reporting procedures.
In addition, the firm had not documented evaluations, investigations, and dispositions of nonconformances; rework and reevaluation activities; and acceptance or rejection activities for in process and finished products. The firm also had not validated production processes, trained employees on the Quality System Regulation, nor had they conducted quality audits. In all, 15 violations of the Quality System Regulation were identified in the Warning Letter.
Consent Decree of Injunction for Multidata Systems International
On May 7, 2003, the FDA announced that the Agency had entered into a consent decree of injunction with Multidata Systems International Corporation (Multidata Systems) to stop them from manufacturing and distributing radiation therapy medical devices. Multidata Systems, headquartered in St. Louis, Missouri, primarily manufactures devices used to treat cancer. The company’s radiation treatment planning software reportedly contributed to 28 patients receiving excessive amounts of radiation at a medical facility in Panama City, Panama, in 2001. Several patients died. Multidata Systems failed to conform to current good manufacturing practice and design standards and also failed to file prompt reports with the FDA after it became aware that its products may have caused or contributed to death or serious injury.
FDA inspected Multidata several times between April 1993 and September 2001 and documented extensive and persistent deficiencies in the firm's manufacturing practices during each inspection.
The firm did not respond to these warnings, and FDA observed the same violations recurring from one inspection to the next. During the inspection preceding the injunction, FDA found that Multidata Systems failed to establish, maintain and follow procedures to control the design of the radiation treatment planning software to ensure the specifications were met; failed to establish and follow procedures for taking preventive and corrective action; failed to establish and follow procedures for investigating all complaints; and failed to adhere to other standard good manufacturing practices. In addition, the firm failed to identify the root cause of software code problems when brought to its attention.
Multidata Systems initiated a recall of its radiation treatment planning software on September 7, 2001, but did not complete the recall until early 2003. The consent decree was filed in the United States District Court for the Eastern District of Missouri, and enjoins Multidata Systems from marketing its radiation therapy medical devices until the firm satisfies FDA that it has corrected its problems.
Civil Money Penalty for Computer Monitor Manufacturer
United States v. ADI Corporation, et al., (N.D. Cal.). On May 9, 2003, U.S. District Judge Vaughn R. Walker signed a Consent Decree for Civil Penalties against ADI Corporation, a Taiwanese manufacturer of computer monitors, and its U.S. and Mexican subsidiaries, ADI Systems, Inc., and ADI Systems Mexico, S.A. DE C.V., respectively. The Complaint alleged that the defendants violated the Radiation Control for Health and Safety Act provisions of the Federal Food, Drug, and Cosmetic Act by distributing in the U.S. more than 55,000 computer monitors that had been certified under a disapproved testing program. The Consent Decree requires an initial penalty of $275,000, which the defendants paid on May 13, 2003, and a final payment of $200,000, due on May 9, 2005.
Sterility Issues Result in Recall
The FDA’s New England District Office reported that Boston Scientific/Microvasive was recalling endoscopic devices. Boston Scientific/ Microvasive, Natick, Massachusetts, initiated a voluntary recall on January 29, 2003, of the Rapid Exchange Retrieval Balloon Distal Injection 8.5 mm balloon and 11.5 balloon size and the Rapid Exchange Biliary System Retrieval Balloon injection, 15 mm balloon due to breach in the sterile packaging barrier. The eleven lots involved in this recall were manufactured in the firm's Cork, Ireland facility. The product is used to endoscopically remove stones from the biliary system or to inject contrast medium while occluding the duct with the balloon.
Recall of Oral Swabs
On November 2, 2003, FDA posted on its website information regarding a recall of oral swabs. Tri-State Hospital Supply Corporation recalled certain kits that contained oral swabs. The kits are called Centurion Mouth Care Kits. The recall was based on information that the sponges on the end of the swabs may come off the handle and could choke the patient. These swabs were also sold under the SHIELD Healthcare Center label as part of enteral feeding kits.
These swabs are often used on very elderly or debilitated patients whose gag responses may be so weak that they can't cough up the sponge if it lodges in their throat. In fact, this recall was initiated after a sponge came off the swab handle and obstructed a patient's airway. These kits were distributed to hospitals nationwide after April 1, 2002. Patients may also have taken them home from a hospital or hospice, and so they may still have them. Tri-State urged these patients to destroy the product because of the potential choking hazard.