Inspections, Compliance, Enforcement, and Criminal Investigations
Philips Medizin Systeme Gmbh 06-May-05
Department of Health and Human Services
Public Health Service
Food and Drug Administration
MAY 6 2005
Mr. Michael Dreher
Managing Director/Director Innovation & Support Service
Philips Medizin Systeme Gmbh
Cardiac and Monitoring Systems
Hewlett-Packard Strasse 2
Dear Mr. Dreher:
During an inspection of your firm located in Boeblingen, Germany, on November 15 through November 18, 2004, our investigator(s) determined that your firm manufactures the lntelliView product family of patient beside monitors (MP20, MP30, MP50, MP70, and MP90) and accessories, including Multi-Measurement Servers. These products are devices within the meaning of section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 321(h)).
This inspection revealed that these devices appear to be adulterated within the meaning of section 501(h) of the Act (21 U.S.C. 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current: Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. Significant violations include, but are not limited to, the following:
1. Failure to establish and maintain adequate procedures for evaluating complaints to ensure uniform and timely processing, as required by 21 CFR 820.198(a). For example:
a. A review of the United States October 2004 customer call database identified 13 of 16 customer call number entries with potential product performance issues, yet none of these resulted in complaint file generation.
b. No evaluation was conducted or documented to determine whether complaints M2004-00491 and M2004-002454 for corrupted time/date stamps, which involved "coded" patients, were reportable to the Food and Drug Administration (FDA) under 21 CFR part 803 or 804, Medical Device Reporting.
c. Complaint No. M2003-000787 (Sp02)/Hypoxia) did not contain information about the allegation of normal Sp02 values and potential correlation with the reported hypoxia.
d. The investigation for complaint M2003-004750, dated May 28, 2003, does not address the reporting user's concerns regarding confusion over the monitor signal and numeric representation at time of death reported.
FDA received responses from Elisabeth M. George, dated December 8, 2004, and January 31, 2005, concerning our investigators' observation 4 noted on the FDA 483. FDA has reviewed your responses and has concluded that they are inadequate for the following reasons. The specific documentation to resolve complaint handling requirements was not provided. To remedy the failure to capture complaints and MDR reportable events from service reports, you plan to update the Service Order Review Requirements (A-Q2920-00161) to enhance linkage with CMS Customer Feedback and Product Incident and Malfunction Report Submission Process (AQ2920- 00153) to ensure that when a death, injury, or malfunction occurs, the factory is notified within 2 business days. You also have conducted retraining of field personnel responsible for the complaint system. FDA will need to review the revised procedures and retraining conducted to determine whether the revisions are adequate to resolve the complaint handling issues. Please provide revised complaint handling procedures, revisions to your Service Order Review Requirements, and evidence of the retraining of employees as well as process updates and further enhancements to the linkage process to prevent future occurrence.
For the latter two items, you indicate that these incidents were missed and you have opened CAPA files which have determined that complaint investigators overlooked the additional information when they performed their investigations. Please provide updated complaint handling and CAPA procedures, linkages between trending and reopening CAPA investigations, evidence of retraining employees, and additional ongoing monitoring that is taking place to prevent future recurrence.
2 . Failure to establish and maintain adequate procedures in order to investigate the cause of nonconformities relating to product, processes, and the Quality System, as required by 21 CFR 820.100(a)(2). For example:
a. CAPA investigation 4921 for complaints M2003-009925 and M2003-010130 received from the same hospital regarding a failure in the arrhythmia analysis software was not further investigated to determine whether similar defects in heart rate monitoring were reported by other facilities. Documentation shows the hazard/ risk index was evaluated as 8=moderate (on a scale of 1-12), the software defect was corrected via a revision for future production, and only the reporting hospital received field action in the form of replacement/upgrade.
b. Complaint M2004-009191, triggering CAPA investigation 5312, regarding a serious "arrhythmia alarms off' malfunction, dated 9/12/2004, disclosed that an additional 18 complaints were received since 1998. Several CAPA investigations were opened and closed for alarm structure problems for the bedside monitors without a complete investigation into a cause of the nonconformity.
c. Complaint number M2003-00787 (Sp02/Hypoxia) regarding a serious injury was not fully investigated to identify potentially related events . The Investigation Template form indicates that this circumstance was unique in response to the question "Does trending suggest action was necessary?," yet a query of the complaint database, searching under "Sp02" yielded approximately 36 complaints which were identified in 2002.
FDA received responses from Elisabeth M. George, dated December 8, 2004, and January 31, 2005, concerning our investigators' observation 3 noted on the FDA 483 . FDA has reviewed your responses and has concluded that they are inadequate for the following reasons. The specific documentation reflected in your reply to Observation 1 has not been provided. FDA will also need to see the results of the present methods of trending to determine the appropriateness of your follow-up to recently opened CAPA files. Please provide the plans for linking the Quality Monitoring Process with the statistical process and the updated complaint procedure as well as evidence that the specific issues have been identified and appropriate corrective and preventive actions have been implemented . Please provide current examples of trending which reflect your follow-up to the CAPA investigations.
3. Failure to establish and maintain adequate procedures that analyze processes and employ appropriate statistical methodology to detect recurring quality problems, as required by 21 CFR 820.100(a)(1). For example:
a. the utilized complaint data analysis methodology is limited to reviewing complaints monthly, by product family, and does not specify the potential causes of the nonconforming product; and
b. the statistical methodology of identifying quality problems for refurbished M3001 A Multi-Measurement Servers has not been established.
FDA received responses from Elisabeth M. George, dated December 8, 2004, and January 31, 2005, concerning our investigators' observation 1 noted on the FDA 483. We have reviewed your responses and have concluded that they are inadequate for the following reasons. The improved documentation to resolve these matters and the associated action triggers or levels were not provided. FDA will need to review the plans for linking the Quality Monitoring Process (A-Q2920- 0192) with the statistical process (A-Q2920-00163). Though you affirmed that reliability of the refurbished devices was equivalent to the new products, no data were provided. The data would need to be reviewed as well as the revised complaint procedure (A-Q2920-00135) which shows how any potential trends that surface with respect to refurbished products are monitored. Please provide the above plans for linking the Quality Monitoring Process with the statistical process and the updated complaint procedure as well as the data showing the equivalency between the refurbished devices and the new products.
4. Failure to establish and maintain adequate procedures in order to identify all actions needed to correct and prevent recurrence of nonconforming product and other quality problems, as required by 21 CFR 820.100(a)(3). For example:
a. the risk to the patient associated with the software failure of the IntelliVue monitor series, which can result in a corrupted time and date stamp was not reevaluated when 6 additional complaints were received; and
b. CMS Health Risk Assessment form for the above corrupted time and data stamp issue was rated as "remote" (no reports in > 1 year) when a total of 49 complaints were received and indicated that this problem had no safety impact when, in fact, 14 of these complaints were classified as safety related. Corrective action(s) to resolve this issue has not yet been completed.
FDA has received responses from Elisabeth M. George, dated December 8, 2004 and January 31, 2005 concerning our investigators' observation 2 noted on the FDA 483. FDA has reviewed your responses and has concluded that they are inadequate for the following reasons . The documentation for reopening or adding to a CAPA investigation was not provided nor was the revision to the risk assessment process included. (A-Q2920-00126 Rev. G), which utilizes both frequency and severity to assign risk and determine a course of action . In addition to these procedures, FDA will need to evaluate the specific health risk and corrective actions for the software failure identified and determine whether resolution has been accomplish with the new process. Please provide the documentation for reopening or adding to a CAPA investigation and the revision to the risk assessment process as discussed above as well as the specific health risk and the corrective actions for the software failures identified.
5. Failure to establish and maintain adequate procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). For example, failure to perform integration testing for software modules used on new product platforms failed to detect corrupted time stamps on bedside monitors and STAR algorithms.
FDA received responses from Elisabeth M. George, dated December 8, 2004 and January 31, 2005 concerning our investigators' observation 5 noted on the FDA 483. FDA has reviewed your responses and has concluded that they are inadequate for the following reasons. The revision to the Design Process procedure (A-Q22920-0204) to allow for enhancement in the handling of integration testing was not provided. Additionally, FDA will need to review corrective action opened to investigate this issue to determine that appropriate follow-up actions were taken where needed. Please provide revisions to the design and development process which enhance awareness to integration of modules across platforms and how you have addressed validation activities. Please further provide documentation that shows evaluation of the same or similar issues across other business units and how such reviews will feed back to the design history file to determine the need for software revalidation.
6. Failure to provide an individual medical device manufacturer report to FDA Form 3500A which included accurate adverse event data elements as required by 21 CFR 803.52. For example, the Block H summary of the returned device evaluation for MDR report number 9610816-2003-000276 does not correspond to the information provided in the Additional Manufacturer Narrative. FDA received responses from Elisabeth M. George, dated December 8, 2004, and January 31, 2005, concerning our investigators' observation 7 noted on the FDA 483. FDA has reviewed your responses and has concluded that they are inadequate for the following reasons. A copy of the corrected MDR record was not provided. In addition to the corrected MDR report, revisions to your procedures should be incorporated into written MDR procedures, and submitted for review. Please provide a copy of the corrected MDR report, evidence of retraining, and revised MDR procedures to prevent future occurrence.
This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious underlying problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.
You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action, which may include detaining your devices without physical examination upon entry into the United States until the corrections are completed (Section 801(a) of the Act (21 U.S.C. 381(a)).
Please notify this office in writing within fifteen (15) working days from the date you receive this letter, of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include all documentation of the corrective action you have taken. If you plan to make any corrections in the future, include those plans with your response to this letter as well. If the documentation is not in English, please provide a translation to facilitate our review.
Your response should be sent to the Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Division of Enforcement B, Cardiovascular and Neurological Devices Branch, 2098 Gaither Road, Rockville, Maryland 20850 USA, to the attention of Leslie E. Caster, Acting Branch Chief.
If you need help in understanding the contents of this letter, please contact John F. Glass at the above address or at (240) 276- 0297 or FAX (240) 276-0129.
Timothy A. Ulatowski
Office of Compliance
Center for Devices and Radiological Health