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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Enforcement Actions

LifeScan, Inc. 07-Dec-05

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

 

San Francisco District
1431 Harbor Bay Parkway
Alameda, CA 94502-7070
Telephone: 510-337-8700



Via Federal Express

2nd copy hand delivered on December 7, 2005 after noting 2 lines missing starting on page 5 of this letter

Our Reference : 2039301

December 7, 2005

Eric P. Milledge
Company Group Chairman
LifeScan, Inc.
1000 Gibraltar Drive
Miipitas, CA 95035-b301

WARNING LETTER

Dear Mr. Milledge:

This letter is in reference to a Food and Drug Administration (FDA) inspection of your establishment located in Milpitas, California, on April 6 - June 30, 2005. In the course of that inspection, our investigators determined that you are manufacturing the OneTouch Ultra and the OneTouch UltraSmart Blood Glucose Meters in violation of the Federal Food, Drug, and Cosmetic Act (the Act).

The OneTouch Ultra and OneTouch UltraSmart Blood Glucose Meters are intended to be used for the quantitative measurement of glucose in fresh capillary whole blood. Accordingly, they are devices as defined in Section 201(h) of the Act because they are intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or because they are intended to affect the structure or any function of the body.

As explained below, our inspection revealed that these devices are adulterated within the meaning of Section 501(h) of the Act, in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformance with the Current Good Manufacturing Practices (CGMP) requirements of the Quality System (QS) regulation, as specified in Title 21, Code of Federal Regulations (CFR), Part 820. In addition, these devices are misbranded within the meaning of Section 502(t)(2) of the Act, in that your firm failed or refused to furnish material or information required by or under Section 519 of the Act and the Medical Device Reporting (MDR) regulations at 21 CFR Part 803.

We acknowledge receipt of your letters dated July 25, 2005, October 6, 2005, and October 20, 2005 written in response to the Inspectional Observations (FDA-483) issued at the close of the inspection. Your July 25 letter was written in response to the QS failures and your October 6 and October 20 letters were written to specifically respond to the MDR violations . We have reviewed the information in your letters and have taken it into consideration prior to the issuance of this letter. Significant deviations were identified during the inspection, including but not limited to the following :

1. Failure to control devices that do not meet specifications as required in 21 CFR 820.80(d). For example, on September 30, 2003 you decided to notify FDA that the OneTouch Ultra Blood Glucose Meters Owner's Booklets [redacted] failed to identify that the Units of Measurement (UOM) can be set to read in mmo/lL or mg/dL. In an October 7, 2003 letter to Center for Devices and Radiological Health (CDRH), you considered the event to be equivalent to a [redacted]. In a letter dated November 21, 2003, CDRH informed you that the event meets a [redacted] classification and to notify the FDA, San Francisco District Office. On that same date, you initiated a field action and issued notification letters to your customers to inform them of the UOM issue and provided an updated booklet. However, you continued to distribute the identical booklets that were subject to a field action until May 18, 2004. As a result 28,954 nonconforming booklets were distributed without information notifying users the meter is capable of displaying the UOM in either mmol/L or mg/dL.

Your July 25, 2005 response failed to provide detailed information covering your corrective and preventive action to ensure that quality system requirements are effectively implemented throughout your organization. Please provide a detailed explanation as to how your firm will ensure the implementation of your internal procedures and that they comply with the Quality System regulation.

2. Failure to review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications, as required in 21 CFR 820.198(c). For example:

  • Consumer Complaint [redacted] Patient's daughter contacted your company to report the OneTouch Ultra was set in the wrong units of .measurement. Complaint was closed without performing an investigation.

  • Consumer Complaint [redacted] Patient contacted your company to report the OneTouch Ultra was set to the wrong units of measurement. Complaint was closed without performing an investigation.

  • Consumer Complaint [redacted] Patient's nurse contacted your company to report the OneTouch Ultra was reading high and patient was taken to the Emergency Room. This complaint was closed without performing an investigation.

  • Consumer Complaint [redacted] Patient contacted your company to report the OneTouch Ultra was reading low. This complaint was closed without performing an investigation.

  • Consumer Complain [redacted] Patient's husband contacted your company to report the OneTouch Ultra was set to the wrong units of measurement. This complaint was closed without performing an investigation.

  • In your July 25, 2005 response, your discussion of these five complaints made no reference to any ongoing failure investigations. Also, our inspection revealed that you have been aware of five factors that can affect the Units of Measure (UOM) setting: [redacted] Four of the five complaints noted above were categorized under [redacted] and you failed to verify known causes of failures or investigate other possible factors that may also contribute to the reported event so that you may adequately assess your corrective actions to date.

3. Appropriate sources of quality data are not adequately analyzed to identify existing and potential causes of nonconforming products and other quality problems, as required in 21 CFR 820.100(a)(1) . For example, on October 15, 2004 LifeScan identified that [redacted] of all complaints received from July 2002 to July 2004 were categorized as [redacted]. During our recent ihs the study results were brought to your attention by the FDA investigator. [redacted] was initiated on April 12, 2005 to investigate the high percentage of [redacted] you have been receiving.

Your July 25, 2005 response and referenced procedures appear to be adequate; however, various corrective actions-have not been completed :

  • Retrospective review of the top ten complaints of all OneTouch Ultra complaints to assess and analyze if investigations performed to date are adequate was scheduled to be completed by [redacted]. As of the date of this letter, the status of this action has no been provided to the District Office.

  • Retrospective review (statistical sampling) of remaining OneTouch Ultra complaints to assess and analyze if investigations performed to date are adequate was scheduled to be completed by [redacted]. As of the date of this letter, the status of this action has not been provided to the District Office.

  • "Triggers" will be built into the complaint handling system to initiate investigation of use-related complaints. This action is not scheduled to be completed until [redacted]

  • A complete review of all Product Analysis test sampling is being conducted to assure a more comprehensive approach for the investigation of returned products. This sampling plan was scheduled for completion by October 31, 2005. As of the date of this letter, the status of this action has not been provided to the District Office.

Please provide the District Office with a copy of all referenced reports upon completion.

4. Procedures were not followed for the identification, documentation, validation or verification, review, and approval of design changes before their implementation as required in 21 CPR 820.30(i). For example, labeling changes were implemented to the OneTouch Ultra's Owner's Booklets and without following your own internal procedure [redacted] (Rev. A. [redacted] ). Numerous changes we Including the removal of language referencing the device's capability of displaying the UOM in either mmol/L or mg/dL, without linking those changes back into design controls.

Your July 25, 2005 response and attached procedures appear to be adequate in addressing the requirements of having a system. However, information leading to the cause of this nonconformity was not provided. It's unclear if you performed an investigation to identify the root cause and how you are going to prevent the recurrence of your employees not implementing company-wide procedures. In addition to the correction identified above, the verification and validation activities for labeling changes made to your other device, the OneTouch UltraSmart, are not scheduled for completion until [redacted]. Please provide the district with an explanation detailing your target completion date in verifying and validating those, design changes.

5. Management with executive responsibility has not ensured that the quality system is understood; implemented, and maintained at all levels of the organization, as required in 21 CFR 820.20.

Your July 25, 2005 response and planned actions appear to adequately address the observation; however, your response identifies the launch and/or implementation of various corrective actions that, as of the date of this letter, have not been completed:

  • Organizational training to be launched by [redacted]. As of the date of this letter, a status report has not been provided to the District Office.

  • Organizational training in risk management and implementation of improvements into existing procedures and processes to be implemented by [redacted]. As of the date of this letter, a status report has not been provided to the District Office.

Please provide the District Office with copies of your, various documents/reports upon completion. In addition to the deviations described above that render your device adulterated, our inspection revealed that your device is also misbranded within the meaning of section 512(t)(2) of the Act, in that your firm failed or refused to furnish material or information required by or under section 519 of the Act and the Medical Device Reporting (MDR) regulations at 21 CFR Part 803.

Specifically, your firm failed to adhere to 21 CFR 843.50(a)(1) and (2), which require device manufacturers to report, within 30 days of receiving or otherwise becoming aware of information, from any source, that reasonably suggests that a device marketed by the manufacturer: (1) may have caused or contributed to a death or serious injury ; or (2) has malfunctioned and such device or a similar device marketed by the manufacturer would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur.

Your firm has also failed to adhere to the requirements of 21 CFR Part 803.50(b)(3), which requires device manufacturers to conduct an investigation of each event including an evaluation of the cause of the event. If you cannot submit complete information on a report, you must provide a statement explaining why this information was incomplete and the steps you took to obtain this information. If you later obtain any required information that was not available at the time you filed your initial report, you must submit this information in a supplemental report under 21 CFR Part 803.56.

Due to the lack of investigation of the reported events, your firm does not have the information necessary to be able to reach a reasonable conclusion that would rule out that your device did not cause or contribute to the event or that your device did not fail to perform as intended. Therefore, your firm has failed to submit MDR reports as required by 21 CFR Part 803 .50, including but not limited to the following instances:

1. The information contained in Service Request [redacted] reasonably suggests that your device may have caused or contributed to a serious injury that necessitated medical intervention to preclude permanent impairment of a body function or permanent damage to a body structure. Your Customer Care Representative reported that the meter was set to the incorrect UOM (mmol/L). Patient thought blood glucose readings were low-and continued to eat sugar to elevate the blood glucose level. Patient went to the hospital and was placed on IV. Although you attempted to. contact the customer with a follow up call and letter, dated [redacted] there is no evidence that additional attempts were made to further investigate this report to obtain missing information or to determine if the device malfunctioned. This complaint should have been reported [redacted] as a serious injury.

2. The information contained, in Service Request [redacted] reasonably suggests that your device may have caused or contributed to a serious injury to the patient that necessitated medical intervention to preclude permanent impairment of a body function or permanent damage to a body structure. Your Customer Care Representative reported that the meter was set to an incorrect unit of measure, as, the caregiver had been misinterpreting 4.0 to 6.0 mmol/L readings as 40 to 60 mg/dL (equivalent to 72 and 108 mg/dL respectively). The patient was admitted to the hospital and treated with [redacted]. There is no evidence that you attempted to further investigate this report to obtain missing information, clarify conflicting information, or to determine if the device malfunctioned. This complaint should have been reported as a serious injury.

3. The information contained in Service Request [redacted] reasonably suggests that your device may have caused or contributed to a serious injury to the patient that necessitated medical intervention to preclude permanent impairment of a body function or permanent damage to a body structure. Your Customer Care Representative received information that the patient had been misinterpreting blood glucose readings (example given was 8.2 mmol/L as 82 mg/dL. Patient was admitted to the hospital because of [redacted]. There is no evidence that you attempted to fur er investigate this report to obtain missing information or to determine if the device malfunctioned . This complaint should have been reported as a serious injury.

4. The information contained in Service Request [redacted] reasonably suggests that your device may have caused or contributed to a serious injury to the patient, that necessitated medical intervention to preclude permanent impairment of a body function or permanent damage to a body structure. Caregiver reported that patient's meter was set to wrong UOM. Result of 28.1 mmol/L (506mg/dl) was interpreted as 281 mg/dl. [redacted] were given for anxiety. Patient became [redacted] with [redacted]. Patient was taken to ER and administered insulin and a CT scan to detect possible [redacted]. Although you attempted to contact this customer with a follow up letter, dated April 18, 2005, there is no evidence that you attempted to further investigate this report to obtain missing information or clarify conflicting information. This complaint should have been reported as a serious injury.

5. The information contained in Service Request [redacted] reasonably suggests that your device malfunctioned. Your Customer Care Representative received information that the meter had been providing readings in mmol/L rather than mg/dL. Based on the readings being received, the patient consumed sugar to increase blood glucose level and was subsequently admitted to the hospital.

Although you attempted to contact the customer with a follow up call and letter, dated April 14, 2005, there is no evidence that additional attempts were made to further nvestigate this report to obtain missing information or to determine if the device malfunctioned. The inaccurate readings represent a malfunction, which could cause or contribute to a serious injury or death if it was to recur.

Our inspection also revealed that your MDR event files do not contain or reference all adverse event information in the possession of the reporting entity, including documentation of the deliberation and decision nuking process used to determine if an event was or was not reportable, as required in 21 CFR 803.18(b)(1)(i).

As you have described in your October 6, 2005 response, the complaints listed above and on the FDA-483 have now been submitted as MDR reportable events. The actions taken to submit these reports appear to be adequate; however, as part of your overall corrective action, your response fails to include a timeline to begin and/or complete your retrospective review of other prior complaints for MDR reportability. You will need to submit your timeline to the District Office. As you stated in your letter, please contact the Office of Surveillance and Biometrics (OSB) for instructions on retrospective MDR reporting prior to the submission of any unreported MDRs you may uncover during your review.

Your October 6, 2005 response also describes the need to validate changes planned for your electronic complaint handling system. Again, a timeline for the completion of your validation study was not provided. The validation of your complaint handling system and the training of your employees are critical to prevent the recurrence of this observation. Without the review of 'your preventive action(s), it is difficult to gauge your compliance to the regulation. Upon the completion of your system validation and the training of your employees to the new complaint handling system, please provide the District Office with your documents.

Your October 20, 2005 response includes a statement that your Medical Affairs staff underwent additional training in classifying and auditing complaints for MDR reportability, and to clearly document the decision making process. However, the specific training provided to your staff, and/or the details covering the actions implemented to prevent the recurrence of this observation was not included in your responses. Please provide the District Office with documentation demonstrating compliance.

Your October 20, 2005 response included the revised Work Instructions ([redacted] and the Medical Device Reporting and Vigilance System General Operating Procedure ([redacted]) which were forwarded to OSB for review. The results of their review will be sent to you in a separate letter .

This letter is not intended to be an all-inclusive list of violations at your facility. It is your responsibility to ensure that all requirements of the Act are being met. The specific violations noted in this letter and in the form FDA 483 issued at the conclusion of the inspection may be symptomatic of serious underlying problems in your firm's manufacturing and quality assurance system . You are responsible for investigating and determining the causes of the violations identified by the FDA. If the causes are determined to be system problems, you must promptly initiate permanent corrective actions.

Federal agencies are advised of the issuance of all Warning Letters so that they may take this information into account when considering the award of contracts. Also, no requests for Certificates of Product for Export will be approved until all violations relating to the subject devices have been corrected.

You should take prompt actions to correct these deviations. Failure to promptly correct these deviations may result in regulatory action being initiated by the Food and Drug .Administration without further notice. These actions include, but are not limited to, seizure; injunction, and/or the imposition of civil penalties.

You should notify our office in writing, within fifteen (15) working days of your receipt of this letter, of the specific steps you have taken or will take to correct these violations and preclude their recurrence. If corrective action cannot be completed within fifteen working days, state the reason for the delay and the time frame within which corrections will be completed. Your response should address each deficiency brought to your attention during the inspection and in this letter, and should include copies of any documentation demonstrating that corrections have been made. Please direct your reply to Lawton W. Lum, Compliance Officer, United States Food and Drug Administration, 1431 Harbor Bay Parkway, Alameda, CA 94502.

Sincerely yours,

/s/
Barbara J. Cassens
District Director
San Francisco District