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U.S. Department of Health and Human Services

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Enforcement Actions

Baxter Healthcare Corporation 23-Mar-05

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

Public Health Service
Food and Drug Administration

 

555 Winderley PI ., Ste. 200
Maitland, FL 32751


CERTIFIED MAIL
RETURN RECEIPT REQUESTED

WARNING LETTER

FLA-05-23

March 23, 2005

Robert L. Parkinson
President and CEO
Baxter Healthcare Corporation
1 Baxter Parkway
Deerfield, Illinois 60015-4625
Dear Mr. Parkinson:


During the October 12-22, 2004, inspection of your establishment located at 7511 114th Avenue, Largo, Florida, an investigator from the Food and Drug Administration determined that your firm manufactures various types of hemodialysis devices. These products are medical devices within the meaning of section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act)(21 U.S .C. 321(h)).

The above-stated inspection revealed that these devices are adulterated under 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, the manufacture, packing, storage, or installation are not in conformance with the Current Good Manufacturing Practice (CGMP) requirements for medical devices, which are set forth in the Quality System regulation . as specified in Title 21, Code of Federal Regulations (CFR), Part 820.

We have received your response to the FDA 483 dated November 11, 2004, and further correspondence dated November 12, 2004, December 17, 2004, January 14 and 31, 2005, and February 11 and 25, 2005; regarding our investigator's observations noted on the FDA 483 issued at the closeout of the Largo facility inspection . Although we acknowledge your firm's efforts to come into compliance with FDA's regulations, you have failed to adequately address the violations noted during this inspection.

Significant deviations found during the October 12-22 inspection include, but are not limited to, the following :

Failure to establish and maintain adequate procedures for implementing corrective and preventive action, which include requirements for verifying or validating corrective and preventive actions to ensure that such actions are effective and do not adversely affect the finished device, as required by 21 CFR 820.100(a)(4) . For example:

A. In February 2000, Baxter generated the Meridian Operator's Manual, which recommended the use of specific qualified bloodlines with the Meridian Hemodialysis machine. The manual stated the following: "WARNING: Extracorporeal tubing sets supplied by Baxter Healthcare are recommended for use on the Meridian instrument. Tubing sets provided by other manufacturers have not been tested by Baxter and cannot be recommended . All tubing sets to be used on the instrument must comply with EN 1283 (CE countries) and meet the specifications provided below". In August 2002, your firm substituted the qualified bloodlines with ones that did not meet the specifications required by the Operator's Manual. Subsequently, the firm received reports of 4 deaths which may have been related to the use of unqualified bloodlines. Additionally, between July and September 2004, your firm received at least 4 incidents reporting the use of unqualified bloodlines resulting in a patient's blood loss of at least 183 cc (serious injury). Your firm sent out an Important Product Information letter dated September 30, 2004, containing the product codes for the Baxter recommended bloodlines to be used with the Meridian Hemodialysis machine; however, your firm did not verify that this letter was effective in informing users of the potential dangers of using unqualified bloodlines, and preventing future recurrences (see FDA 483 observation #3a).

Problems related to the use of unqualified bloodlines have been observed at both the McGaw Park and Largo facilities . Due to the fact that the same problem is occurring at different facilities, we are concerned that your firm's corrective and preventive actions (CAPAs) may be inadequate and appear to be a systemic problem throughout your organization.

Your response to this observation appears to be inadequate because although we acknowledge that you have taken action to resolve the problems associated with the use of unqualified bloodlines. You have failed to provide any supporting documentation that would indicate that you have in fact implemented the actions mentioned in your response. Specifically, you have failed to provide a copy of the November 30, 2004 letter that was or will be sent to Baxter Meridian customers, copies of the initiated CAPAs associated with the above mentioned issues, and any other appropriate documents, as part of your response.

B. Safety Alert Letters dated September 19 and 20, 2002, were issued to inform the users (home care coordinators and patients) of the Homechoice Peritoneal Dialysis (PD) machines of a software anomaly that could potentially cause patient overfill. On September 27, 2002, your firm submitted an implementation plan which proposed the need for a software upgrade to correct the overfill issue and prevent its future recurrence. According to the implementation plan, the software upgrade was planned to be released in February 2003, and a proactive recall of the devices used by the pediatric population was to be conducted within three months of its release : however the software was not released until June 2003, and some of the pediatric patient devices were not upgraded until eight months after the release. From October 2002 to August 2003, your firm received six more Medical Device Reports (MDRs) regarding this issue. Your firm failed to take adequate corrective and preventive action and to verify that the software upgrade was effective in preventing the recurrence of patient overfill issues (see FDA 483 observation #36).

Your response to this observation appears to be inadequate because, although we acknowledge that you are currently working on resolving the software anomalies associated with the Homechoice Peritoneal Dialysis machines, you have failed to provide any supporting documentation that would indicate that you are in fact in the process of resolving these issues . Please provide us with a copy of the plan of action your firm will utilize to effectively resolve these issues and prevent their recurrence .

C. Between January 2001 and January 2004, your firm received thirty-eight incidents reporting the appearance of air bubbles in the extracorporeal blood circuit during use of the Meridian Hemodialysis machine without activating the air detector alarm. In 2003, your firm updated the Meridian Operator's Manual warning users of the potential air bubble issues associated with the use of the Meridian Hemodialysis machine. Additionally, an Urgent Device Correction Letter dated March 11, 2004, was sent to customers instructing them on how to reduce the risk of introducing air bubbles into the extracorporeal blood circuit during hemodialysis, and indicating that Baxter was actively pursuing enhancement of the Meridian's air detection system to increase its sensitivity. Your firm failed to take adequate corrective and preventive action, as the upgrade of the Meridian air detection system had not been implemented up to the time of the current FDA inspection (October 2004)(see FDA 483 observation #3c).

Your response to this observation appears to be inadequate because, although we acknowledge that you have taken action to correct this deficiency, you have failed to provide copies of any supporting documentation that would indicate that you are in fact in the process of resolving these issues and/or have already implemented the corrective actions mentioned in your response. Please provide a copy of the necessary documentation confirming that the actions mentioned in your response have been or will be effectively implemented.

D. Your firm sent a letter dated August 4, 2000, warning all hemodialysis physicians that a possible dislodgement of venous needles or cannulas can occur without activating the alarm, and that this can result in serious patient injury or death. Your firm also indicated that the decrease in pressure resulting from dislodgement is not sufficient to trigger the alarm, and that careful monitoring of the patient for any evidence of extracorporeal blood loss is required to prevent serious injury or death. Additionally, your firm issued a Safety Alert Letter dated September 27, 2004, regarding the venous needle or cannula dislodgement problem. Your firm continued to receive MDRs relating to this issue. Your firm failed to verify that the August 2000 and September 2004 letters were effective in preventing venous dislodgement and thus serious injuries (see FDA 483 observations #3d and #3e).

Your response to this observation appears to be inadequate because, although we acknowledge that you have taken action to correct this problem, you have failed to provide copies of any supporting documentation that would indicate that you are in fact in the process of resolving these issues and/or have already implemented the corrective actions mentioned in your response. Please provide a copy of the necessary documentation confirming that the actions mentioned in your response have been or will be effectively implemented.

E. In January 2002, your firm began to notice problems with the System 1000 device meeting air detection specifications ; however, your firm did not take corrective and preventive action until October 2002, when the devices were placed on hold. In the January 9, 2003 Baxter Renal Service Bulletin and the May 25, 2003 Important Product Information Letter, your firm instructed technicians and customers to check the voltage of the devices in the field and to install an attenuator in case the voltage was out of range, in order to restore the air detector sensitivity. Your firm received complaint #30015227 dated July 16, 2003, which referenced two incidents where air was introduced into the patients' bloodlines without activating the System 1000 air detection alarm. One of the incidents required the patient to be hospitalized . Your firm failed to verify that these corrective and preventive actions were effective in preventing air detection problems (see FDA 483 observation #3f).

Your response to this observation appears to be Inadequate. Although we acknowledge that you are currently working with the Chicago District Office to ensure this issue is adequately addressed and that you have opened a CAPA to address the issues concerning the timeliness of implementing Corrections and Removals, you have failed to explain how your firm will utilize the information obtained as a result of the CAPA investigations opened after the October inspection of the Largo facility. In other words, you have failed to indicate if your firm will use the results of these investigations to implement any design changes, labeling changes, or perform any other pertinent corrective and/or preventive actions related to the System 1000 machines.

F . Your firm received complaint #30011303 dated November 15, 2002, which referenced a patient who was taken to the emergency room and intubated after treatment with the System 1000 Hemodialysis machine. Your firm had previously sent an Urgent Product Recall Letter dated October 23, 2000, to the users of the System 1000 Hemodialysis machine indicating the appearance of problems with the control button for the level adjust pump. More specifically, the letter stated that if the pre-pump arterial drip chamber was in use and the control button got stuck, air may be driven towards the patient. Finally, your firm indicated that the control system had been changed in order to eliminate this potential issue. Your firm failed to verify that the corrective and preventive action referenced in the October 23, 2000 letter was taken, and that it was effective in preventing the recurrence of these types of problems (see FDA 483 observation #3g).

Your response to this observation appears to be inadequate. Although we acknowledge that you have opened a CAPA to address the issues concerning the timeliness of implementing Corrections and Removals, you have failed to indicate how your firm will utilize the information obtained as a result of the CAPA investigations opened after the October inspection of the Largo facility. In other words, you have failed to indicate if your firm will use the results of these investigations to implement any design changes, labeling changes, or perform any other pertinent corrective and/or preventive actions related to the System 1000 machines.

G. Your firm received complaint #30018700 dated February 23, 2004, which referenced a home patient experiencing an overfill problem while using the Homechoice Peritoneal Dialysis machine. Your firm sent an Urgent Device Correction Letter dated May 24, 2004, instructing peritoneal dialysis nurses on how to avoid overfill problems with the Homechoice machines. Your firm indicated that the software release to correct this problem was not scheduled until February 2005. Your firm failed to take adequate corrective and preventive action to prevent future recurrence of patient overfill issues (see FDA 483 observation #3h).

Your response to this observation appears to be inadequate because, although we acknowledge that you have opened CAPAs to investigate the issue and develop technical solutions to resolve this problem, you have failed to indicate how your firm will utilize the information obtained as a result of these investigations. Additionally, you have failed to provide any documentation demonstrating your firm's commitment to resolve these issues. Please provide a copy of the necessary documentation confirming that the actions mentioned in your response have been or will be effectively implemented.

H. Your firm received complaint # 30012936 dated February 27, 2003, which referenced a home patient complaining that, on three different occasions, the 1550 Hemodialysis unit failed to remove the correct ultrafiltrate weight from the patient. On February 27, 2003, Baxter personnel found that the deaeration system was not thoroughly removing air from this 1550 Hemodialysis unit, resulting in erroneous weight removals. The technician did not have the necessary equipment to replace the deaeration system at the time of the visit. Additionally, your firm received complaint #30013058 dated March 7, 2003, which referenced the same home patient complaining about the same ultrafiltrate weight removal issue. All of the aforementioned incidents were reported to FDA as separate MDR events . Your firm did not replace the deaeration system until the March 7, 2003 complaint was received. Your firm failed to take adequate corrective and preventive action, in that the technician did not replace the deaeration system until the fourth MDR event occurred (see FDA 483 observation #3i).

Your response to this observation appears to be inadequate because, although we acknowledge that you have taken action to correct this problem, you have failed to provide copies of any supporting documentation that would indicate that you are in fact in the process of resolving these issues and/or have already implemented the corrective actions mentioned in your response . Specifically, you have failed to provide copies of the revised Servicing procedure, as part of your response. Please provide a copy of this revised procedure and any other appropriate documents.

2. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, which include requirements for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product or other quality problems. Appropriate statistical methodology shall be employed where necessary to detect recurring quality problems, as required by 21 CFR 820.100(a)(1). For example:

A. Your firm received nine incidents of needles becoming dislodged as part of complaint #30009003 dated July 3, 2002. Your firm did not provide documentation demonstrating that these nine incidents were analyzed as multiple incidents, rather than as just one complaint (see FDA 483 observation #6a).

B. The complaint information your firm receives is not being analyzed by failure modes; and your firm's MDRs are not being analyzed for problems occurring at the Largo facility (see FDA 483 observation #6b).

Your response to these observations appears to be inadequate because, although we acknowledge that you have taken action to correct these problems. You have failed to provide copies of any supporting documentation that would indicate that you are in fact in the process of resolving these issues and/or have already implemented the corrective actions mentioned in your response. Specifically, you have failed to provide copies of the Largo procedure RG0076 "Quality Improvement and Process Management Teams", as part of your response. Please provide a copy of this procedure and any other appropriate documents.

3. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, which include requirements for investigating the cause of nonconformities relating to product, processes, and the quality system, as required by 21 CFR 820.100(a)(2) . For example, your firm began to notice problems with the System 1000 machines meeting air detection specifications as early as January 2002; however, your firm did not place these devices on hold until nine months later, in October 2002 (see FDA 483 observation #3f).

Your response to this observation appears to be inadequate . Although we acknowledge that you are currently working with the Chicago District Office to ensure this issue is adequately addressed and that you have opened a CAPA to address the issues concerning the timeliness of implementing Corrections and Removals, you have failed to indicate how your firm will utilize the information obtained as a result of the CAPA investigations opened after the October inspection of the Largo facility. In other words, you have failed to indicate if your firm will use the results of these investigations to implement any design changes, labeling changes, or perform any other pertinent corrective and/or preventive actions related to the System 1000 machines.

4. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, which include requirements for identifying the action(s) needed to correct and prevent recurrence of non-conforming product and other quality problems, as required by 21 CFR 820.100(a)(3). Specifically, in February 2000, Baxter generated the Meridian Operator's Manual, which recommended the use of specific qualified bloodlines with the Meridian Hemodialysis machine. The manual stated the following: "WARNING: Extracorporeal tubing sets supplied by Baxter Healthcare are recommended for use on the Meridian instrument. Tubing sets provided by other manufacturers have not been tested by Baxter and cannot be recommended . All tubing sets to be used on the instrument must comply with EN 1283 (CE countries) and meet the specifications provided below". In August 2002, your firm substituted the qualified bloodlines with ones that did not meet the specifications required by the Operator's Manual ; however, your firm failed to perform a risk analysis on the implemented change, and therefore failed to verify that such change would correct and prevent the recurrence of quality problems (see FDA 483 observation #4).

Your response to this observation appears to be inadequate because, although we acknowledge that you have taken corrective action to mitigate the problems associated with the use of unqualified bloodlines, you have failed to provide any supporting documentation that would indicate that you have in fact implemented such actions Specifically, you have failed to provide a copy of the November 30, 2004 letter that was or will be sent to Baxter Meridian customers . copies of the initiated CAPAs associated with the above mentioned issues and any other appropriate documents, as part of your response. Please provide a copy of the initiated CAPAs, the November 30th letter, and any other appropriate documents.

5. Failure to establish and maintain adequate procedures for validating the device design. Design validation shall include software validation and risk analysis where appropriate as required by 21 CFR 820.30(g) . For example, complaint #30017315 dated October 23, 2003, referenced a software anomaly of the Renalsoft Software Suite, which resulted in the delivery of the wrong medication to one or more patients. Specifically, the user did not use the add button, but added the medication totals directly to the database, accidentally overwriting and substituting the requested drug in all of the individual patient records. Your firm failed to identify this problem during the design validation phase of the manufacturing process (see FDA 483 observation #2).

Your response to this observation appears to be inadequate because, although we acknowledge that you are currently working on deploying new software for use with the Renalsoft Software Suite, you have failed to provide any concrete evidence (i.e. documentation) that would indicate that you have or will in fact implement this upgrade. Please provide a copy of the necessary documentation confirming that the actions mentioned in your response have been or will be effectively implemented.

6. Failure to maintain adequate complaint files; and when an investigation is made under this section, an adequate record of the investigation shall be maintained by the formally designated unit, as required by 21 CFR 820.198. For example state whether qualified or approved bloodlines were used with the appropriate dialysis devices. Specifically, it was observed that in at least fifteen incidents, your firm failed to identify which dialysis device was used with which type of bloodline. Additionally, on at least three occasions, your firm did identify the dialysis machine and type of bloodline used, but failed to determine whether the bloodline was qualified for use with the subject dialysis machine, as referenced in complaint #s 30020794 and 30015227 (see FDA 483 observation #7a).

Your response to this observation appears to be inadequate because you have failed to indicate whether twelve of the fifteen complaints referenced in the FDA 483 were investigated as necessary to identify the dialysis machines involved in each particular incident. Specifically, your firm's response states that three of the fifteen complaints had been corrected ; however, it fails to state whether the other complaints were also corrected, followed-up on, or closed out.

Medical Device Reporting

The above-stated inspection also revealed that your devices are misbranded within the meaning of section 502(t)(2) of the Act (21 U.S.C. 352(t)(2)), in that your firm failed or refused to furnish any material or information required by or under section 519 of the Act respecting the device, including the Medical Device Reponing regulation (21 CFR Part 803) and/or the Reports of Corrections and Removal regulation (21 CFR Part 806).

1 . Your firm failed to submit MDRs within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device may have caused or contributed to a death or serious in injury, as required by 21 CFR 803 .50(a)(1). For example:

A. Complaint #30020794 dated July 2, 2004, concerned a report from [redacted] that a leak in the pump segment of the Medisystems blood tubing 5M6605 was noted one hour and 20 minutes into treatment. A cut found one inch from the inlet connector caused air to be pulled into the system. The tubing and dialyzer were discarded with a blood loss of 183cc. This event should have been reported to FDA as a serious injury within 30 days of the date your firm was alerted (see FDA 483 observation #5a).

B. Complaint #30021281 dated August 26, 2004, from [redacted] included a report that on August 25, 2004, a cut in the pump segment of the Medisystems blood tubing 5M6605 resulted in air being drawn into the bloodlines approximately one to one and a half hours into the treatment. The treatment was stopped and the tubing was discarded with a loss of approximately 200cc of blood. This incident should have been reported to FDA as a serious injury within 30 days of the date your firm was alerted (see FDA 483 observation #5b).

Your response to these observations appears to be inadequate because you have failed to provide a copy of the MDRs your firm reportedly submitted for Complaints #30020794 and #30021281 . Although your firm's response indicates that you submitted these MDRs on October 14, 2004 and October 15, 2004 respectively, a review of our records does not confirm this submission . Please provide a copy of the submitted MDRs.

2. Your firm failed to submit a written report of any correction or removal of a device that you initiated if the correction or removal was initiated to reduce a risk to health posed by the device, as required by 21 CFR 806.10(a)(1) . For example:

A. Your firm failed to report to FDA the field action started with the January 9, 2003 Baxter Renal Service Bulletin, and followed by the May 28, 2003 Important Product Information Letter, which instructed technicians and customers to check the voltage of devices in the field and to install an attenuator if the voltage was out of range. The action was initiated in response to an investigation conducted in 2002, which revealed that System 1000 devices did not meet air detection specifications. Additionally, a shipment hold was placed on these devices from October 2002 to October 2004. Your firm failed to document the reason for not reporting this action as a corrections and removal event (see FDA 483 observation # 1a).

Your response of this observation appears to be adequate.

B. Your firm received complaint #30006423 dated January 21, 2002, which referenced air being observed in the patient's bloodlines without triggering the air detection alarm of the System 1000. It was found that the introduction of air bubbles was the result of loose arterial and venous level adjust valves: and that the air detector system failed to meet specifications. In May 2003, your firm implemented a new testing procedure, which was included in the System 1000 Service Manual; however, this was not reported to FDA as a corrections and removal event (see FDA 483 item #1b).

Your response to this observation appears to be adequate.

C. Your firm received complaint #30007803 dated April 18, 2002, which referenced a Meridian Hemodialysis machine catching fire at the power entry module. The complaint further stated that the nurse received a mild shock when checking the device . A Baxter technician confirmed that the power cord was arcing . The technician then replaced the power entry module and cord. Baxter addressed the defect by adding a new bracket to support the connection of the power cord. This addition was reported in the September 13, 2002 Service Bulletin. Your firm failed to report this action as a corrections and removal event (see FDA 483 observation # 1d).

Your response to this observation appears to be adequate.

D. Your firm received complaint #30015421 dated July 29, 2003, which referenced a home patient who received an electric shock when he pressed the power switch to the off position . The event was reported as an MDR in 2003. Your firm determined that the switch should be redesigned to include an extra terminal for grounding purposes. Your firm failed to report this action as a correction and removal event. Although the event was not initially reported, your firm indicated that according to the "FCA Executive Summary & Rationale" dated October 2004, the complaint would be reported as a Correction or Removal event. This action has not yet been reported to the FDA (this event was not included in the FDA 483).

This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and regulations. The specific violations noted in this letter and in the FDA 483 issued at the close 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 and for promptly initiating permanent corrective and preventive action on your quality system.

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, no premarket submissions for Class ill devices to which Quality System regulation deficiencies are reasonably related will be cleared until the violations have been corrected. Also, no requests for Certificates to Foreign Governments will be approved until the violations related to the subject devices have been corrected. You should take prompt action 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 civil penalties.

Please notify this office in writing within fifteen (15) working days of receipt of this letter, of any steps that you are still in the process of taking to correct the noted violations, including (1) the time frames within which the corrections will be completed, (2) any documentation indicating the corrections have been achieved, and (3) an explanation of each step being taken to identify and make corrections to any underlying systems problems necessary to assure that similar violations will not recur.

Your response should be sent to the Food and Drug Administration, Florida District, 555 Winderley Place, Suite 200, Maitland, Florida 32751, to the attention of Timothy J. Couzins.

If you need help in understanding the contents of this letter, please contact Timothy J. Couzins, Compliance Officer, at the above address or at (407) 475-4728.

Sincerely,
/s/

Emma R. Singleton

Director, Florida District