Philips Medical Systems (Cleveland) Inc 6/7/11

 

Department of Health and Human Services	Public Health Service Food and Drug Administration
	Cincinnati District Office Central Region 6751 Steger Drive Cincinnati, OH 45237-30977 Telephone: (513) 679-2700         FAX: (513) 679-2761

 

                                                                                                                                                                               

 

June 7, 2011

 

VIA UNITED PARCEL SERVICE

 

WARNING LETTER CIN-11-158993-19

 

Jonathan J. Mazelsky

Sr. V.P. and GM of CT/NM

Philips Medical Systems (Cleveland) Inc.

595 Minor Road

Cleveland, OH 44143-2131

 

Dear Mr. Mazelsky:

 

During an inspection of your firm located in Cleveland, OHon August 25, 2010 through December 3, 2010, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures Brilliance, Big Bore, iCT, and the MX-16 Slice Families of CT products; and Gemini, Gemini LXL/TF, BrightView, JetStream, and Precedence Families of NM products. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices 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 are intended to affect the structure or function of the body.

 

This inspection revealed that these devices are 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. We received responses from Joseph A. Vinhais, Senior Director CT/NM Quality and Regulatory dated December 23, 2010, February 28, 2011, and March 31, 2011 concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address these responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:

 

1. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a).

 

For example, defect CTUDT00184880 was initiated on 11/18/09, due to the wrong HCOR Scaling for Infant basic body scans on a Brilliance 64 system. Your firm identified a hazard of misdiagnosis as an "Unacceptable" risk level. The error was identified when updating from the Brilliance 2.4.6 software package to Brilliance 2.6 software at three beta sites. The identified solution was to recalibrate with an infant phantom on 11/26/09. This issue was not managed through the CAPA system but rather through the Defect. The Defect report shows that this corrective action of recalibrating the sites was "verified" on 2/22/10. Your firm did not implement the fix until 3/2/10 at one beta site and 7/8/10 (nearly 8 months later) at another.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has performed a risk assessment of the Field Change Order (FCO 72800521) that resulted from the corrective action mentioned in the observation using the Health Hazard Evaluation (HHE) process and determined the risk to be unacceptable. Your firm filed a Field Action Decision Form (FADF) with the FDA to correct the observation. Your firm has identified the systemic root cause of the observation to be tied to External Validation process. As such, your firm is revising the External Validation process to clearly define the requirements for External Validation activities from start to finish. In addition, your firm has identified as part of your corrective action, the need for assessing work instructions, aligning of various quality system processes, the assessment of open and closed validation records, development of instructor lead training, and a review of External Validation process IT tools. Your firm has provided a correction to the observation and has identified the systemic deficiency that resulted in the observation. The planned revisions, however, have not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

2. Failure to adequately implement and record changes in methods and procedures needed to correct and prevent identified quality problems, as required by 21 CFR 820.100(a)(5). 

 

For example, two complaints (292365 and 329346) were filed at your firm related to smoke over a four month period regarding fire and/or a burning electrical smell emitting from Anode/Cathode power modules as a result of EMI board failures due to moisture ingress. Complaint 292365 resulted in the filing of an MDR on 11/3/09. The anode/cathode power modules are supplied to your firm by (b)(4). Your supplier identified in a memo dated 2/5/10, that DI water used to wash the printed circuit boards may have caused the issue (moisture ingress). Your supplier's manufacturing solution was to introduce a baking process to remove the moisture, which was implemented on 2/18/10. Your firm received the first corrected anode/cathode power modules on 2/26/10 and they were consumed in production by 3/11/10. Between 2/5/2010 through 3/11/2010 your firm continued to use 264 anode/cathode power modules with unbaked boards with no documented rational for continuing to use EMI boards after root cause was determined and a correction implemented.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has performed a review of failures associated with the Anode Power Module (APM) and Cathode Power Module (CPM) that were distributed despite the identified moisture ingress issue and found a total of 5 complaints out of 9000 units in the field related to the APM, CPM, or EMI boards. CAPA #486261 was opened to confirm that no additional field action was required. No additional action has been identified to date. Your firm’s investigation identified that the CAPA process lacked a complete and consistent method for CAPA data source identification and methodology, evaluation of nonconformities within CAPA subsystems, root cause investigation, CAPA planning and implementation and CAPA effectiveness measures. Your firm’s action plan includes revision of the CAPA procedure including implementation of a CAPA review board, alignment of CAPA process and interdependent processes, implementation of a CAPA assessment tool, development of remediation protocol for open and closed CAPA records, developing and conducting instructor based training on revised processes, and review and alignment of CAPA IT tools. The planned revisions, however, have not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

3. Failure to investigate the cause of nonconformities relating to product, process, and the quality system, as required by 21 CFR 820.100(a)(2). 

 

For example, CAPA 10-020 was issued on 7/30/10 regarding button artifacts associated with three recent complaints (CTCPa00003315, CTCPa00003468, and PR ID: 284825). This issue was identified in a previous CAPA (IR03106 dated 11/30/07) which resulted in a field correction. To date there has been no documentation regarding the investigation or a determination of root cause.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has performed a review of the three complaints (CTCPa00003315, CTCPa00003468, and PR ID: 284825) and determined that the complaints were not related to the previous CAPA that drove the field correction. As such, your firm has updated CAPA 10-020 to include an explanation of CAPA issuance document the results of the investigation and subsequent closure. Your firm’s investigation identified that the CAPA process lacked a complete and consistent method for CAPA data source identification and methodology, evaluation of nonconformities within CAPA subsystems, root cause investigation, CAPA planning and implementation and CAPA effectiveness measures. Your firm’s action plan includes revision of the CAPA procedure including implementation of a CAPA review board, alignment of CAPA process and interdependent processes, implementation of a CAPA assessment tool, development of remediation protocol for open and closed CAPA records, developing and conducting instructor based training on revised processes, and review and alignment of CAPA IT tools. The planned revisions, however, have not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

4. Failure to establish and maintain adequate procedures to verify the design of the device in order to ensure that design output meets the design input requirements specified, as required by 21 CFR 820.30(f). 

 

For example, a review of 23 design inputs associated with the Condor CT/PET system, (Condor Customer Requirements Specification Rev. F, dated 08/24/09) showed that 5 of the design inputs either did not meet specification, were not adequately tested, or did not show quantifiable results.

• Requirement GEMCR1332 identifies that the latency of respiratory tags registration (latency in the correlation of event data with the respiratory triggers) shall be no longer than (b)(4). This parameter was not met, as the analysis for Respiratory Tag Latency (XNGV-0380058) identifies a limit of (b)(4), no documentation exists to explain why this is acceptable.
• Requirement GEMCR1661 identifies that the reconstruction times on PET images shall be less than 10 minutes. The Condor reconstruction protocol verification test (VERTC4010) shows times that would indicate the system originally failed the test on 4/6/09 with a total time (b)(4) for a parameter limited at (b)(4). Per Design Verification - Validation procedure BLSOP-043 Rev 00, the test should have been marked failed and a defect report opened and identified on the test sheet. This was not done. The test was re-run and was marked as passed later that day with no explanation of why the test failed or what was changed to make the test pass.
• Requirement GEMCR18 identifies the system be able to reconstruct PET images with a reconstructed field of view of at least (b)(4). Per VALTC917 the Operator Actions are listed as running "general system" protocols (XNGN-0370406/XNGN-0370377) for the test. The actual test only ran a Condor specific protocol (XNGN0370630) and marked the test as passed.
• Requirement GEMCR457 identifies that when the system is in a closed configuration the PET and CT components be separated by at least (b)(4). This was marked as passed in VERTC2391 and VALTC1439 with no recorded value.
• Requirement GEMCR495 identifies that the gating scheme perform over a range of (b)(4). This validation test was never conducted as this test (VALTC1463) was associated with a previous failed verification test (VERTC3890). VERTC3890 failed due to missing connecters required to test the system, this was captured by defect report NMDBa00027439. The defect report only addressed the missing connectors and their installation, not the testing or re-testing of the system. There is no explanation how this test (VALTC2463) passed. 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has performed a review of the nonconformities and your firm determined that neither the individual tests, nor an aggregation of these tests, prevent the system's intended use, or compromise its safety and effectiveness. Additionally, your firm is still reviewing and updating the investigation of 5 of the 12 identified requirements as part of the initial correction. Your firm's investigation found that the design requirements and verification processes do not contain sufficient infrastructure to ensure consistent execution of the requirements and verification activities. Your firm's action plan involves revising requirement procedures to include a review process to determine the adequacy of test cases, alignment of Design Change, Defect Management and Design Validation processes with updates to Design Inputs and Design Verification/Validation processes, developing and conducting instructor-led training on revised processes, Product Training, Good Documentation Practices (GDP), and reviewing Design Inputs and Verification/Validation process IT tools. The planned revisions, however, have not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

5. Failure to establish and maintain adequate procedures to validate the design of the device in order to ensure that the device conforms to defined user needs and intended uses, as required by 21 CFR 820.30(g).   

 

For example, a review of 23 design inputs associated with the Condor CT/PET system, (Condor Customer Requirements Specification Rev. F, dated 08/24/09) showed that 7 of the design inputs either did not meet specification, were not adequately tested, or did not show quantifiable results.

• Requirement GEMCR1338 identifies that three different types of retrospective PET scan acquisitions be implemented. Only two acquisitions, a respiratory gated CT scan for CTAC and a respiratory gated PET scan in accordance with Validation Test Case 2650 (VALTC2650), were tested and recorded.
• Requirement GEMCR1349.12 includes that waveform statistics related to the period, amplitude, and full inhalation/exhalation location is available to the user. Verification Test Case 4807 (VERTC4807) states that among other things internal average and standard deviation, amplitude average and standard deviation be available to the user. On 4/8/09, the system failed the requirements of VERTC4807 for not displaying the standard deviations, defect NMDBa00025399 was created to address this issue. To date this issue has not been resolved and has been postponed to a later design. The subsequent Validation Test Case (VALTC2193) was "passed" on 8/4/09 even though there were defects found and a defect report had been initiated as a result of previously failed verification testing.
• Requirement GEMCR1922 identifies a system sensitivity shall be greater or equal to 6000 cps/MBq. VALTC3099 documents that on 8/25/09 this test failed. A defect report (NMDBa00029183) was opened 8/27/09 which stated that the defect can remain open but continues to need to be worked on. To date there is no evidence that this issue is being addressed.
• Requirement GEMCR22 identifies that the maximum vertical position variation relative to the system laser reference marker be (b)(4) for all patients in allowable weight range. VALTC934 failed on 8/7/09, resulting in the filing of defect report NMDBa00029061. The defect report states that the test was addressed as part of a Random Regression & Stress Test Worksheet (XNGN-0370557) completed 4/8/09. There are no records of the results from this testing.
• Requirement GEMCR1659 identifies that the CT Gantry physical patient aperture be at least 85cm. The test (VALTC3020) was passed with no documentation of the actual measured value on 7/31/09.
• Requirement GEMCR320 as tested by VALTC600 identifies testing a torso phantom while setting the rate to (b)(4) (to mimic heart rate) for a cardiac PET acquisition. The system was tested (VALTC600) at (b)(4) and passed with no explanation why this was acceptable.
• Requirement GEMCR1505 identifies that the system be able to display images that are viewable on a Gemini 3.3 or later version. The system was tested (VALTC2216) and passed with no documentation of which system was tested.

We have reviewed your responses and have concluded that they are inadequate. Your firm has performed a review of the nonconformities and your firm determined that neither the individual tests, nor an aggregation of these tests, prevent the system's intended use, or compromise its safety and effectiveness. Your firm has not addressed the deficiency observed with regard to inadequate validation testing or documentation of validation results.

 

6. Failure to ensure that the risk analysis is performed where appropriate during the design validation, as required by 21 CFR 820.30(g). For example:  

 

A. A review of the risk analysis surrounding the Condor Big Bore NM device showed that not all hazards associated with the device were entered into the Risk Management Summary (RMS) for the device. There were two defects found during verification testing, defect NMDBa00027443 which identified an inability to hear the response of individuals in the PET gantry and defect NMDBa00028653 which identified beta site Condor cross hairs that do not intersect. These defects introduced new hazards which were not added to the RMS. The identified risks were: that a patient may not be heard at the control console and that the lasers used for land mark identification do not intersect.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm performed an audit of the Condor defects on 11/08/2010 to capture the observed hazards. Your firm's investigation identified that the Risk Management process and its relationship to the CAPA, Defect Management, Complaint Handling, and Adverse Event Reporting and Corrections and Removals processes did not include measures to ensure that any new hazards or risks identified throughout the product's lifecycle were added to the Risk Management File. Your firm's action plan includes revising and creating (as needed) CT/NM Risk Management procedures to ensure regulatory compliance and linkages to interdependent processes (CAPA, complaint handling, defect management, corrections and removals, adverse event reporting, nonconforming product, equipment controls, internal auditing, management reviews), developing and conducting instructor-led training on revised procedures, creating of Hazard/Harm Matrix to be used in Complaint Handling and Adverse Event Reporting, and reviewing Risk Management process IT tools. The planned revisions, however, have not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

B. The Work Management Work Instruction procedures (NMC-31 0, Rev C) describe that only hazards with a risk greater than a combined total of 12 (expressed as a risk product number or RPN score) are evaluated for addition into the RMF. This score is calculated as severity (1-4) x Probability (1-6) x detectability (1-4) = RPN. During the investigation, your firm re-evaluated the RPN scores associated with this project in Condor Defect Risk Analysis Audit (XNGR0383904 Rev A) and found that only 64% of the original scores remained the same. Twenty-three percent of the reviewed defects were evaluated to have decreased RPN, and the remaining 13% received an increased RPN that required evaluation for addition into the RMF.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. The Risk Management File for Condor Big Bore NM Device #XNGN-0380018, Revision 04, was revised to include hazards identified during the development cycle, regardless of the RPN. Therefore, all identified hazards are captured in the RMF. Your firm's investigation identified that the Risk Management process and its relationship to the CAPA, Defect Management, Complaint Handling, and Adverse Event Reporting and Corrections and Removals processes did not include measures to ensure that any new hazards or risks identified throughout the product's lifecycle were added to the Risk Management File. Your firm's action plan includes revising and creating (as needed) CT/NM Risk Management procedures to ensure regulatory compliance and linkages to interdependent processes (CAPA, complaint handling, defect management, corrections and removals, adverse event reporting, nonconforming product, equipment controls, internal auditing, management reviews), developing and conducting instructor-led training on revised procedures, creating of Hazard/Harm Matrix to be used in Complaint Handling and Adverse Event Reporting, and reviewing Risk Management process IT tools. The action plan, however, has not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

7. Failure to validate a process with a high degree of assurance in accordance to an established and approved procedure where the process cannot be fully verified by subsequent inspection and test, as required by 21 CFR 820.75(a). For example:

 

A. Your firm has not validated the degassing procedure (NMEP-3685 Rev A) for variables such as pressure and time. In addition, your firm is not monitoring or recording these parameters. 

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm completed the validation of the degassing/gluing process on 02/17/2011. During the validation, your firm contracted a third party to provide oversight for process. Your firm's investigation into the systemic deficiency identified that the process validation process was not consistently applied to production processes. Therefore, your firm's action plan involves revising the process validation procedure, revising design transfer procedures to ensure linkage and alignment with the revised process validation procedure, conducting instructor-led process validation training, completing the Manufacturing Validation Plan for CT/NM product lines to determine if additional process validations are required, and conducting any additional process validations. The action plan, however, has not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

B. Deviations were found (spikes in image quality) in the gluing Validation Test Plan Report (DHF116846 Version 01) which are required to be addressed, evaluated, and accepted or rejected by your firm’s Manufacturing Process Validation procedure (BLSOP-025 Rev A). These deviations were not addressed in the report (DHF116846) or any subsequent document.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has revised the process validation procedure to address the items identified in the gap analysis performed for BLSOP-025. Training was completed on the new procedure on 02/16/2011. Your firm's investigation into the systemic deficiency identified that the process validation process was not consistently applied to production processes. Therefore, your firm's action plan involves revising the process validation procedure, revising design transfer procedures to ensure linkage and alignment with revised process validation procedure, conducting instructor-led process validation training, completing Manufacturing Validation Plan for CT/NM product lines to determine if additional process validations are required, and conducting any additional process validations. The action plan, however, has not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

C. Acceptance criteria for the "pull test" (to test glue strength at specific drying times) values were not defined prior to conducting the studies.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has completed the validation of the degassing/gluing process on 02/17/2011. During the validation, your firm contracted a third party to provide oversight for process. Your firm's investigation into the systemic deficiency identified that the Process Validation process was not consistently applied to production processes. Therefore, your firm's action plan involves revising the Process Validation procedure, revising Design Transfer procedures to ensure linkage and alignment with revised Process Validation procedure, conducting instructor-led process validation training, completing Manufacturing Validation Plan for CT/NM product lines to determine if additional process validations are required, and conducting any additional Process Validations. The action plan, however, has not been fully communicated or approved through your firm’s approval process and the implementation of the required changes and training has not been performed.

 

D. Your firm performs a soldering operation to repair PCBs (Printed Circuit Boards) for NM devices which fail during final assembly and testing. All boards are manufactured by contract manufacturers. Your firm has not validated this soldering process, shown that the type of solder (b)(4) used to repair boards is equivalent to that solder (b)(4) used during production, or that the solder used does not adversely affect the device.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm completed a retrospective soldering process validation on 02/17/2011, and no issues were found to necessitate a field action. Standard Soldering Rework Procedure (NMEP-3509) was updated as a result of the validation activity and personnel trained on 01/24/2011. In addition, your firm has indicated that in-house soldering will no longer take place. Your firm's investigation into the systemic deficiency identified that the process validation process was not consistently applied to production processes. Therefore, your firm's action plan involves revising the process validation procedure, revising design transfer procedures to ensure linkage and alignment with revised process validation procedure, conducting instructor-led process validation training, completing Manufacturing Validation Plan for CT/NM product lines to determine if additional process validations are required, and conducting any additional process validations. Your firm’s action plan includes changes to improve the soldering validation procedure, but has indicated in its response that in-house soldering will no longer take place. Your firm, however, has not provided evidence of implementation of all of their corrective actions.

 

8. Failure to establish and maintain adequate requirements, including quality requirements, that must be met by suppliers, contractors, and consultants that define the type and extent of control to be exercised over the product, services, suppliers, contractors, and consultants, based on the evaluation results, as required by 21 CFR 820.50(a)(2). For example:

 

A. Your firm reported the failure of a CPM module to your supplier on 10/8/08. According to a memo from your supplier dated 9/21/09, "This failure was supposed to be highlighted and investigated further by the supplier". This was not done by the supplier at that time. Additionally, similar failures were reported to the supplier regarding instances on 10/08 and 8/09. This similar failure resulted in two MDR reports by your firm. No root cause was reported to your firm until 2/5/10 by the supplier. During this time, your firm did not apply any additional inspectional activities, increased oversight, or evaluate any additional suppliers for this part. Additionally, your firm did not initiate a supplier corrective action (SCAR) per procedures BLSOP-095 Rev B for an identified supplier defect. 

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. As part of the correction your firm performed a retrospective SCAR (102700) which was created in order to properly document the previous activities relative to this observation issue and ensure they were effective. The SCAR was sent to your supplier,   (b)(4)     , on 12/10/2010per Supplier Corrective Action and Preventative Action Process BLSOP 095 Rev. B. In addition, your firm reviewed all current Manufacturing Defect Reports (MDR) to determine the need to escalate reports into SCARs. The review determined that retrospective SCARs were not necessary. Your firm's investigation into the systemic deficiency identified that the supplier controls processes (including Supplier Corrective Action and Supplier Qualification processes) did not exercise adequate controls over suppliers to ensure overall product quality. Your firm's action plan consists of revising the supplier controls processes, aligning CAPA subsystems and interdependent processes to ensure consistent and cohesive overall assessment and processing of supplier related nonconformities, generating list of component/part specifications with risk rankings, assessing need for remediation of open and closed records relating to this observation (e.g., supplier files and SCAR records), develop and implement remediation protocol if required per assessment results, developing and conducting instructor-led training on revised processes and Good Documentation Practices (GDP), and reviewing supplier controls process IT tools. The systemic corrective actions identified still require approval, verification, and implementation.

 

B. According to Supplier Quality Program SOP (BLSOP-031, Rev D), a supplier Profile/Self assessment questionnaire is to be filled out for all Consultants, Contractors, Manufactures and Distributors. This form is required as part of supplier evaluations. A review of 17 supplier files showed that: Ten of the forms (59%) were not completed under the "Method of Approval/Phase-out section" which describes the level of control for the supplier. Six out of the ten files contained a "Letter to File" written by the Senior Manager of Supplier Quality essentially waiving this requirement. There are no provisions within any of the supplier management procedures which allow for an individual to waive supplier qualifications. Additionally, the remaining 4 files had no self assessment questionnaire or "Letter to File".

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. As part of the correction your firm has reviewed the 17 supplier files cited for completeness and verified them to be complete, the method of approval has been clearly defined for the 10 suppliers, and the supplier self assessments that were missing were obtained and added to the file. Your firm's investigation into the systemic deficiency identified that the supplier controls processes (including Supplier Corrective Action and Supplier Qualification processes) did not exercise adequate controls over suppliers to ensure overall product quality. Your firm's action plan consists of revising the supplier controls processes, aligning CAPA subsystems and interdependent processes to ensure consistent and cohesive overall assessment and processing of supplier related nonconformities, generating list of component/part specifications with risk rankings, assessing need for remediation of open and closed records relating to this observation (e.g., supplier files and SCAR records), develop and implement remediation protocol if required per assessment results, developing and conducting instructor-led training on revised processes and Good Documentation Practices (GDP), and reviewing supplier controls process IT tools. The systemic corrective actions identified still require approval, verification, and implementation.

 

9. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).   

 

For example, according to Regulatory and Approbation Complaint Handling Procedure XCTW-0341105 Rev. L, the complaint coordinator is to enter complaints within one business day of receipt and Complaint Handling Process BLSOP-079 Rev: C, which states that complaints are to be entered into the complaint system within two business days. A review of 37 complaint files revealed that 17 complaints were not filed within the established time limits. Among these 17 complaints, the following four were not entered as or managed as a complaint for a month or longer after the incident date.

• Complaint 358953 documents that your firm was informed of reported artifacts in Slab Viewer on 12/9/09, but did not open a complaint until 4/22/10 (more than four months later).
• Complaint 404949 documents that your firm was made aware of a reported clear block artifact on 6/22/10, but did not open a complaint until 8/18/10 (nearly two months later).
• Complaint 347680 documents that your firm was informed of a pixel artifact on 12/8/09, but did not open a complaint until 3/24/10 (more than three months later).
• Complaint 364812 documents that your firm was informed of an issue with identifying liver volume on 4/1/10, but did not open a complaint until 5/10/10 (over one month later).

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. As part of the correction your firm now conducts weekly key word searches on service records in accordance with the Service Order Review procedure (XI-060010 dated January 6, 2010). Your firm's investigation identified that the Service Call Center and Service Records processes did not include mechanisms to ensure that all nonconformities meeting the definition of a complaint were identified or routed through the Complaint Handling Process. Your firm's action plan involves revising the CT/NM Complaint Handling procedures, revising procedures for interdependent processes in accordance with complaint handling requirements, developing and conducting instructor-led training on revised processes, reviewing Complaint Handling IT process tools, and investigating Potential IT monitoring solutions will be investigated to facilitate timely complaint creation. The systemic corrective actions identified in the action plan have not been completed, approved, or implemented yet.

 

10. 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 by 21 CFR 820.198(c). For example:  

 

A. From 8/1/2009 - 9/1/2010 there were 27 Defect Reports for computer tomography (CT) systems (found in clinical use) that have been identified by your firm as complaints which were not entered into your firm's complaint system and thus were not managed as complaints. Examples of these defect reports include:

• Defect CTUDT00189668 initiated on 1/14/10 describes that batch reference lines do not correspond to the real batch. The firm has identified this issue as a hazard in the defect report.
• Defect CTUDT00177876 initiated on 8/20/09 describes that a life sync error causes the E-Stop to open and this can happen at any time including during a scan. The firm has identified this issue as a hazard in the defect report.
• Defect CTUDT00188358 initiated on 12/30/09 describes that when loading a cardiac helix scan to CCA (Comprehensive Cardiac Analysis) that was sent from the scanner on the Portal server with the ECG wave, where a message stating, "cannot find one or more slices on the server. Please rebuild database. CCA will now close". This defect did not have a hazard identified.

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. As part of the correction your firm performed an analysis of all engineering defects to confirm that defects that meet the definition of a complaint have been entered into the complaint system. In addition, the cited defects have been entered into the complaint system and independent Q&R weekly audits of the engineering defect database are being performed to make certain that defects are appropriately entered into TrackWise. The investigation performed by your firm to address the systemic deficiency identified inadequate complaint handling processes that did not ensure complete and consistent handling of complaints and complaint data sources. Your firm will be modifying the complaint handling process to improve identification of potential complaint data sources, clarify definition of complaint, improve the requirements for information gathering and complaint evaluation, initial risk assessment, define criteria to determine need for root cause, and the development of Hazard/Harm matrix to facilitate complaint handling. The systemic corrective actions identified by your firm are under evaluation and require approval, implementation, and training which has not been completed yet.

 

B. During the same time frame from 8/1/2009 - 9/1/2010 there were an additional 23 Defect Reports for nuclear medicine (NM) systems (found in clinical use) which your firm has identified as complaints but have not yet been entered into your firm's complaint system. Examples of these defect reports include:

• Defect NMDBa00027915 initiated on 4/13/09 describes that the activity concentration scaling factor could give a different value than that embedded in the DICOM file for PET systems. Your firm has identified this issue as a hazard in the defect report.
• Defect NMDBa00030868 initiated on 3/1/10 describes that the current design of the flat pallet guiderail is not as robust as required and that one has broken in the field. Your firm has identified this issue as a hazard in the defect report.
• Defect NMDBa00029627 initiated on 10/12/09 describes that two set screws used on the table were missing from the upper and lower pallets causing the lower pallet to jump gear teeth.

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. As part of the correction your firm performed an analysis of all engineering defects to confirm that defects that meet the definition of a complaint have been entered into the complaint system. In addition, the cited defects have been entered into the complaint system and independent Q&R weekly audits of the engineering defect database are being performed to make certain that defects are appropriately entered into TrackWise. The investigation performed by your firm to address the systemic deficiency identified inadequate complaint handling processes that did not ensure complete and consistent handling of complaints and complaint data sources. Your firm will be modifying the complaint handling process to improve identification of potential complaint data sources, clarify definition of complaint, improve the requirements for information gathering and complaint evaluation, initial risk assessment, define criteria to determine need for root cause, and the development of Hazard/Harm matrix to facilitate complaint handling. The systemic corrective actions identified by your firm are under evaluation and require approval, implementation, and training which has not been completed yet.

 

C. Additionally, the investigation revealed the following complaints that were entered into the complaint system, but have no documented evaluations for investigations or rationale for not investigating.

• Complaint 385750 initiated on 7/9/10 regarding image quality issues with Dynamic Dose Modulation (DDOM) on a Brilliance 64 CT system.
• Complaint 342464 initiated 2/22/10 regarding an MXTwin that was reported to emit a burning smell and smoke.
• Complaint 353508 initiated 4/8/10 regarding a Brilliance 40 CT system where part of the CT unit began to smoke.
• Complaint 389776 initiated 7/20/10 regarding Brilliance 64 where the transistor unit caught on fire.
• Complaint 385818 initiated 6/2/09 reports that an MX-8000 CT scanner caught on fire.

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. As part of the correction your firm has updated complaints #385750, 342464, 353508, 389776, and 385818 in the system for completeness. The updates were completed on 2/15/2011. The investigation performed by your firm to address the systemic deficiency identified inadequate complaint handling processes that did not ensure complete and consistent handling of complaints and complaint data sources. Your firm will be modifying the complaint handling process to improve identification of potential complaint data sources, clarify definition of complaint, improve the requirements for information gathering and complaint evaluation, initial risk assessment, define criteria to determine need for root cause, and the development of Hazard/Harm matrix to facilitate complaint handling. The systemic corrective actions identified by your firm are under evaluation and require approval, implementation, and training which has not been completed yet.

 

11. Failure to promptly review, evaluate, and investigate any complaint that represents an event which must be reported to FDA under part 21 CFR 803, as required by 21 CFR 820.198(d). For example:    

 

A. Complaint 298784, was initiated on 11/2/09 in response to a user who was severely shocked by the circuit breaker in an MX 8000 while the CT system was reenergizing. The breaker was reported to trip after table positioning was used (raising or lowing the table). The circuit breaker and a vertical motor were replaced in the field for the unit. An MDR was filed on 11/18/09. Your firm did not investigate this complaint to determine the root cause. 

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. The investigation performed by your firm to address the systemic deficiency identified inadequate complaint handling processes that did not ensure complete and consistent handling of complaints and complaint data sources. Your firm will be modifying the complaint handling process to improve identification of potential complaint data sources, clarify definition of complaint, improve the requirements for information gathering and complaint evaluation, initial risk assessment, define criteria to determine need for root cause, and the development of Hazard/Harm matrix to facilitate complaint handling. The systemic corrective actions identified by your firm are under evaluation and require approval, implementation, and training which has not been completed yet.

 

B. Complaint 376831, was initiated on 3/1/10 in response to a customer complaint (reported by a Physician) of totally unacceptable images since the 3.5.1 upgrade for the Pulmo gating studies regarding Gemini PET CT systems. It was reported by your firm that this defect could give false negatives in patients. Your firm did not create a complaint record until 6/15/10 (over 3 months to create the file). Your firm subsequently reported an MDR (late) on 9/2/10 (MDR 2010-00026).

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. The investigation performed by your firm to address the systemic deficiency identified inadequate complaint handling processes that did not ensure complete and consistent handling of complaints and complaint data sources. Your firm will be modifying the complaint handling process to improve identification of potential complaint data sources, clarify definition of complaint, improve the requirements for information gathering and complaint evaluation, initial risk assessment, define criteria to determine need for root cause, and the development of Hazard/Harm matrix to facilitate complaint handling. The systemic corrective actions identified by your firm are under evaluation and require approval, implementation, and training which has not been completed yet.

 

12. Failure to establish and maintain adequate procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a).   

 

For example, 2 out of 21 testing bay notebooks were reviewed during this inspection. These notebooks are used to record information during the final assembly and testing of both the computer tomography (CT) and nuclear medicine (NM) product lines, in their respective bays. Per your firm’s Non-Conforming Material Control Processes SOP (XCTW-0504004, Rev B1) and Initial Data Entry Process for Manufacturing Defect Reporting Database SOP (NMC-405, Rev. M), any defects found during testing must be documented under a Defect Report. The review of the two bay notebooks revealed a total of 24 entries (10 from the bay 5 notebook and 14 from bay 14 notebook) which constitute defects (nonconforming material) and have no associated manufacturing defect report (Defect Report) as required by the firms procedures. As such, these defects are not being trended, included for potential corrective actions or included as part of the device history record(s).

 

We have reviewed your responses dated 12/23/2010, 2/28/2011, and 3/31/2011 and have concluded that the adequacy of the responses cannot be determined at this time. As part of the corrections and corrective actions your firm has performed the following activities:

• A product hold and stop shipment, was issued against NM and CT products (respectively) in process at the time that the bay books were in use.
• A review of the DHRs for the identified suspect NM units has been completed on 12/23/2010 and it was determined that all testing was found to be complete and accurate.
• A review of the CT DHRs for the suspect CT units was completed. No issues were identified for units in production but the analysis did identify the need for corrections on 2 units in the field.
• Pre-Installation Procedure #1651 was revised to eliminate bay books. Training was conducted on 12/01/2010.
• An audit of all log books (bay books) in-house to ensure that any suspected product quality issues were resolved adequately. No issues were identified for units in production but the analysis did identify the need for corrections on 2 units in the field.
• Revisions were made to your Nonconforming Product procedures and training was completed on 12/15/2010 and 2/17/2011.

Your firm found during the investigation that nonconformities identified during Inspection and Test were not always included in the Device History Record. Your firm’s action plan consists of revising CT/NM Control of Nonconforming Product procedures, aligning interdependent processes, including Inspection and Test/Acceptance and DHR procedures, to the revisions of the Control of Nonconforming Product procedure, assessing need for remediation of open and closed records, developing and conducting instructor-led training on revised processes, Good Documentation Practices (GDP) and defect awareness, investigating alternative method for shift change communication and updating procedures accordingly, and reviewing nonconforming product process IT tools. Not all of the systemic corrective actions identified in the action plan have been completed or implemented yet. 

 

13. Failure to establish and maintain adequate procedures to control all documents, as required by 21 CFR 820.40.   

 

For example, there are 21 manufacturing test bays at your firm for testing and final assembly of all CT and NM systems. Each of these bays has an associated testing bay notebook which is maintained by the technicians. These books contain information relating to defects and failures associated with the devices during testing. According to your firm’s Quality Manual QM-00 Rev P, “Records must remain legible, readily identifiable, and retrievable, and must be stored to minimize deterioration and prevent loss.” These books, however, are not controlled by your firm, do not follow your firm's document control procedures, and are destroyed after they are filled. In addition, a review of the notebooks showed that:

• White out is used to cover over data
• Original data is obliterated
• There are no initials or dates for line out items

According to your firm, employees are trained to not cover over data and to initial and date any changes or line through.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. As part of the correction your firm removed all bay books for analysis and replaced them with an alternative method of communication between technicians and shift changes.In addition, production personnel were retrained on Good Documentation Practices on 12/18/2010 and 2/4/2011. Your firm's investigation determined that the inspection and test process did not effectively reinforce good documentation practices or identify all potential sources of nonconformities. The action plan consists of developing Good Documentation Practices procedure, revising Control of Quality Records procedures in accordance with the Good Documentation Practices, developing and conducting instructor-led training on revised Good Documentation Practices and Control of Quality Records procedures, and Review related process IT tools. The systemic corrective actions identified in the action plan have not been completed, approved, or implemented yet. 

 

14. Failure to ensure that all documents are reviewed and approved by a designated individual prior to issuance and that documents are available at all locations for which they are designated, used, or otherwise necessary, and all obsolete documents are promptly removed from all points of use or otherwise prevented from unintended use, as required by 21 CFR 820.40(a).   

 

For example, documents that were not approved were observed at a location where they are being used. Specifically, the Philips Healthcare Supplier Profile Database was changed in June 2010 to alter the parameters used for managing the suppliers in the database. As of October 5, 2010, the work instruction for this database (UXW-141710 Rev 2) was still being used at your firm’s Cleveland, OH facility with no documented official release or approval.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. As part of the correction to the observation your firm revised the Supplier Profile Database (SPD) Management procedure (UXW-141710, Rev 2) on 10/28/2010and personnel were trained on 12/17/2010. Your firm's investigation into the systemic deficiency found that the document control process did not provide a transitioning mechanism to ensure effective implementation of process changes. Your firm's action plan includes revisions to the process which include oversight by a change control board. The change control board is in the process of being developed and established. The systemic corrective actions identified in the action plan have not been completed, approved, or implemented yet.

 

15. Failure to establish and maintain adequate procedures to ensure that mix-ups, damage, deterioration, contamination, or other adverse effects to product do not occur during handling, as required by 21 CFR 820.140.   

 

For example, during assembly of all devices your firm utilizes storage bins in order to retrieve the correct part number to manufacture the NM and CT devices. A sampling of 16 of these bins showed that 9 (56%) of them had multiple incorrect parts in the bins. The bins sampled were mostly assorted types of screws, bolts, nuts and washers. The differences in these parts was not always easily apparent as among other things, split washers were found with regular washers, different sized diameter washers were intermixed and different screw sizes were intermingled. None of your firm's standard operating procedures address the control of these bins. In addition, Mr. Vinhais, Director of Quality and Regulatory, indicated that no procedures describing control of these bins existed.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has performed an analysis of complaints, installation defects, and rectory defect reports and determined that no mixed material has been used inappropriately in a product. Additionally, the material storage bins have been modified to include a cover and similarly sized and shaped components are no longer stored next to each other. Employee awareness training to the new changes was completed on 2/16/2011. Your firm's investigation into the systemic deficiency found that processes for handling material in production do not adequately address materials staging, procurement, handling, component stock returns, or specials or the identification of production material, including segregation, labeling and storage. Your firm's action plan includes investigating alternative materials storage and handling requirements. The systemic corrective actions identified in the action plan have not been completed, approved, or implemented yet.

 

16. Failure to ensure that all personnel are trained to adequately perform their assigned responsibilities, as required by 21 CFR 820.25(b).For example:

 

A. Employees performing incoming inspectional activities were not trained on the statistical sampling plan for Receiving Inspections (BLSOP-092 Rev: A). A review of 7 inspectional activities which required a sampling for inspection revealed that two of the inspections were not sampled properly. According to your firm, there are 4 people who can and do perform this function, however, none of these employees were trained on the procedures. 

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm trained the required personnel on procedure BLSOP-092 on 12/19/2010. In addition, your firm has performed an investigation into the cited nonconformity and found that training was incomplete for an additional nineteen (19) documents and is in the process of completing the additional training. Your firm’s action plan includes, revising the CT/NM training procedure, reviewing and revising interdependent procedures in accordance with new CT/NM Training procedure, developing and conducting instructor-led training on revised procedures, and developing and implementing a "train the trainer" program. The action plan provided is in process and has not been completed or implemented.

 

B. On 10/13/10 an employee was observed working on the Brilliance 16 Big Bore CT line not wearing an electro static discharge (ESD) bracelet, which prevents damage to electrical components from static electricity, while working on the system. The bracelet is required for the step number 170 of Operation 70. This requirement is addressed in training and documented in the legend for the Operation procedure (OPERATION 70 - ACCOLADE, document #2011 Rev: J) and identified in yellow at any step requiring it in the procedure.

 

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has implemented a correction to the observation and has provided personnel with refresher ESD training. Your firm’s investigation into the cited nonconformity found that ESD controls did not sufficiently ensure the proper handling and identification of ESD sensitive material. With regards to ESD protocol, your firm intends to conduct an audit of all current ESD controls in place, including equipment, to ensure they meet the requirements of the new procedures, revise manufacturing ESD control procedures, revise Preventative Maintenance (PM) and Inspection, Test and Calibration procedures to ensure that test equipment required for ESD tools are included in PMI calibration schedules.   The action plan provided is in process and has not been completed or implemented.

 

Our inspection also revealed that your devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 CFR Part 803 - Medical Device Reporting (MDR) regulation. Significant deviations include, but are not limited to, the following:

 

Failure to report to the FDA no later than 30 calendar days after the day you became aware of information that reasonably suggests that your device malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur, as required by 21 CFR 803.50(a)(2). 

 

For example, the following complaints describe MDR reportable events that were not submitted to FDA within 30 days after the day you became aware of the event:

• Complaint 371160;
• Complaint 389776;
• Complaint 385818;
• Complaint 275356;
• Complaint 351042;
• Complaint 325458; and
• Complaint 358511.

We have reviewed your responses and have concluded that the adequacy of the responses cannot be determined at this time. Your firm has completed a review to confirm that all complaints noted in the observation have been reported and that any additional complaints have also been appropriately reported. Your firm identified that the mechanisms for Adverse Event Reporting did not assure accurate evaluation of adverse events. Process revisions are underway to address Reporting Criteria determination, timely evaluation, definitions related to reporting, complaint handling, improve linkages to interdependent processes, and the development/use of Hazard/Harm matrix in conjunction with risk management files to facilitate accurate adverse event reporting. Modifications and training need to be fully identified and implemented.

 

Our inspection also revealed that your devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 CFR Part 806 – Reports of Corrections and Removals regulation. Significant deviations include, but are not limited to, the following:

 

Failure to submit a report of a correction or removal within 10 - working days ofinitiating such correction or removal, as required by 21 CFR 806.10(b).

 

For example, on 9/3/09, your firm received complaint 284929 regarding improper calculations of cardiac wall thickness during imaging studies in the Extended Brilliance Workstation for Computed Tomography (CT) systems. The root cause was determined to be an improper calculation in the software. Your firm sent a customer notification letter to all affected sites in October 2009. This action was not reported to the FDA.

 

We have reviewed your responses and have concluded they appear to be adequate. Your firm has submitted Recall 152965-09129/1 0-005-C to the FDA and submitted the documentation required by 21 CFR 806.20 to the District Recall Coordinator. Your firm identified the systemic root cause to be that the procedures for Corrections and Removals and Field Change Orders (FCO) were inadequate to ensure that recall activities and regulatory reporting requirements were addressed in a timely and complete manner. Revisions were made to the Corrections and Removals And Field Change Order processes to improve reporting and documentation requirements, classification of recalls, and linkages to interdependent processes that could identify non-conformities that could result in a recall. The changes were communicated to appropriate personnel on 02/08/2011.

 

You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly correct these violation(s) 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 civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

 

We are requesting that you submit to this office on the schedule below, certification by an outside expert consultant that he/she has conducted an audit of your establishment's manufacturing and quality assurance systems relative to the requirements of the device QS regulation (21 CFR, Part 820). You should also submit a copy of the consultant's report, and certification by your establishment's Chief Executive Officer (if other than yourself) that he or she has reviewed the consultant's report and that your establishment has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections and subsequent certifications of updated audits and corrections (if required) should be submitted to this office by the following dates:

• Initial certifications by consultant and establishment – December 7, 2011.

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 violation(s), or similar violation(s), from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.

 

Your response should be sent to: Mark E. Parmon, Compliance Officer, Cincinnati District, 6751 Steger Drive, Cincinnati, OH 45237-3097. If you have any questions about the content of this letter please contact Mark Parmon at (513) 679-2700, Ext. 2162, or (513) 679-2773 (fax).

 

Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) 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 problems in your firm’s manufacturing and quality assurance systems. You should investigate and determine the causes of the violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance. 

 

 

Sincerely yours,

/S/                                                           

Teresa C. Thompson

District Director

Cincinnati District

 

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