Inspections, Compliance, Enforcement, and Criminal Investigations
Boston Scientific Corporation 25-Jan-06
Department of Health and Human Services
Public Health Service
One Montvale Avenue
CORPORATE WARNING LETTER
VIA FEDERAL EXPRESS
January 25, 2006
Mr. James Tobin
President / CEO
Peter M. Nicholas
Boston Scientific Corporation
One Boston Scientific Place
Natick, MA 01760-1537
Dear Mr. Tobin and Mr. Nicholas:
The Food and Drug Administration (FDA) recently performed inspections of Boston Scientific Corporation (BSC) at three separate facilities. The inspections were performed at Natick, MA on July 27 through August 26, 2005; at Maple Grove, MN on July 22 through August 25, 2005; and at Spencer, IN on August 25 through September 12, 2005. These inspections covered your Vaxcel, Enteryx, and Taxus Paclitaxel drug eluting stent products and your Leveen Needle Electrode product. Under the Federal Food, Drug and Cosmetic Act (the Act), these products are devices because they are intended to be used to diagnose or treat a medical condition.
These three FDA inspections each revealed serious regulatory problems involving your medical devices.
As you are aware, FDA recently issued BSC three Warning Letters relating to serious deficiencies identified during inspections at three other BSC facilities. The first Warning Letter was issued on May 18, 2005, regarding your Watertown, MA facility. This Warning Letter discussed, among other items, the failure of your organization to have an adequate quality management system as required by Title 21 Code of Federal Regulations (21 CFR) Part 820. The second Warning Letter was issued on August 1, 2005, for your Glens Falls, NY facility, and the third Warning Letter was issued on August 10, 2005, regarding your Quincy, MA facility. Each of these Warning Letters identified serious, systemic problems with your overall corporate quality management systems.
The purpose of this letter is to apprise top management of your inadequate corporate-wide corrective action plan as evidenced by the continuing serious deficiencies identified at each of these facilities and to remind you of your responsibility to ensure that all facilities continuously comply with the Act and all pertinent regulations.
We request a prompt meeting with your firm. For this meeting, you should come prepared to discuss your current corporate strategy to bring all of your facilities into compliance. You should also come prepared to discuss the recent recalls at your facilities and your ongoing corporate efforts to prevent the recurrence of these violations.
The three most recent inspections at your Natick, MA (NATICK), Maple Grove, MN (MAPLE GROVE) and Spencer, IN (SPENCER) facilities revealed that the devices manufactured at these sites are adulterated under section 501(h) of the Act, 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 QS regulation, as specified in 21 CFR Part 820. FDA has found ongoing systemic violations in the quality management system employed to ensure the safety and effectiveness of the medical devices you distribute. Significant deviations from the QS regulations include, but are not limited to, the following:
1. Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of 21 CFR Part 820 and the firm's established quality policy and objectives, as required by 21 CFR 820.20(c).
As you know, this violation was also described in our previous Warning Letters. This recurring serious deficiency with your corporate quality management is significant. As explained below, changes made to your corporate quality system as detailed in your responses to the recent Warning Letters fail to adequately correct the systemic quality problems and assure that an effective quality system is in place.
Specifically, the failure to monitor incoming complaints for quality issues and trends is a serious failure of your management system. Examples of this violation during the recent inspections include, but are not limited to, the following:
It was observed that as of August 26, 2005, the final day of our inspection at your NATICK facility, your firm was still not trending quality data on incoming complaints for Enteryx products sold and distributed by your firm.
Also, during the inspection at NATICK, it was determined that the facility is still only trending three areas: (1) the number of complaints received per month; (2) the time from receipt of complaint to complaint close; and (3) the time from receipt of complaint sample to complaint close.
During this same inspection, we reviewed all of the complaints received by BSC for your Enteryx product, from January 2005 through July 2005. There was no documentation of any trends regarding the hazard of a potential transmural injection occurring with the use of your Enteryx product.
Following the NATICK inspection, you informed FDA on September 23, 2005, that you were instituting a recall of your Enteryx product based on at least eleven (11) complaints and subsequent MDR's that related to a potential hazard of a transmural injection with this product. The eleven complaints that were the basis for your recall were not part of any trending analysis reviewed by FDA during our inspection at your NATICK facility. Trending of quality data of product complaints is important to ensure that a timely recall is instituted when necessary.
Your SPENCER facility is identified as a Complaint Investigation Site (CIS) that is responsible for tracking and trending complaints of products manufactured at that facility. During the inspection at SPENCER, it was observed that seven complaints relating to "roll-off" time for the Leveen Needle Electrode had been received from January 2005 to May 2005. We observed that all seven of these complaints merely included a statement that read, "No conclusions could be drawn regarding either the validity or possible root cause for this complaint." These seven complaints were not adequately investigated to identify possible trends (i.e., "a roll off" issue).
On August 17, 2005, FDA was notified by BSC Corporate (NATICK) of a recall of the Leveen Needle Electrode. However, during our inspection of the SPENCER facility on August 29, 2005, management representatives stated that they were unaware that the Leveen Needle Electrode product was part of a corporate BSC field action. Hence, the BSC investigation by another BSC facility of a serious complaint (#656988) involving the Leveen Needle Electrode did not include informing SPENCER management (CIS for this product) of the recall action, nor did it allow for a review of actual manufacturing records.
Our May 18, 2005 Warning Letter regarding your Watertown facility also included a violation of 21 CFR 820.20. In that Warning Letter, we expressed our concern that "the responsibilities of quality problems of your Vaxcel product line, including complaints, are shared by at least five different Boston Scientific Corporation facilities. Process requirements and written procedures are not consistent at the facilities that handle the Vaxcel product line to ensure that an effective quality system has been established and maintained."
In your responses to that Warning Letter, you indicated that as of June 2005, BSC trending would be performed by product family or issue. Your firm explained that two corporate CAPA's were initiated on June 2005 in response to these very problems: (1) corporate CAPA CM 523 to correct the problems identified in your complaint handling system and (2) corporate CAPA CM 524 to correct the problems identified in the trending problems that were observed at your firm.
Your response letters dated September 15, 2005 and October 14, 2005, further reported that the majority of tasks were completed for these two CAPA's. You explained that an audit (CC520) was conducted in response to corporate CAPA 523. This audit focused on product lines that are multi-site manufactured and concluded that procedures "contain sufficient guidance to ensure that complaint handling and investigation practices for all businesses/product families with multiple manufacturing site interaction are appropriate and harmonized." Your conclusion that your complaint handling and investigation practices are appropriate and harmonized is questionable, as we continue to see significant problems in these important quality system functions of your firm.
Your actions indicate that you have just focused on the written procedures and have failed your obligation to sufficiently assess the quality oversight that this regulation requires to assure that an effective quality system is established for all products. Failing to assess that the actual complaints and events are being reviewed by all of your separate BSC facilities represents a serious deficiency with your overall corporate quality management system.
2. Failure to review, evaluate, and investigate any complaint involving the possible failure of a device to meet any of its specifications, as required by 21 CFR 820.198(c).
The inspection of your SPENCER facility revealed that you did not adequately investigate the activities involving the Leveen Needle Electrode to determine whether this device failed to meet its specifications. (See item 1 above.) All seven complaints were considered closed. No investigation was performed by SPENCER management because a lot number was not included with the complaint. Therefore, there was no review of any device history record nor were there any trends documented for the "roll off" issues that were being seen by this facility for the Leveen Needle Electrode.
In SPENCER, we also observed that complaints are closed after 90 days because product was not returned and a lot number was not recorded.
3. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit to ensure complaints are processed in a uniform and timely manner, as required by 21 CFR 820.198(a)(1).
Your SOP indicates that a complaint should be documented within [redacted] hours or less of "becoming aware" of the complaint. In NATICK, however, there were inconsistencies in the dates you used as an alert date or when you "become aware" of a complaint.
Specifically, we observed time differences that ranged from 4 weeks to 11 1/2 months after you first became aware of the complaint.
4. Failure to promptly review, evaluate, and investigate complaints representing events that must be reported to FDA under part 803 (i.e., are MDR reportable) by designated individuals, as required by 21 CFR 820.198(d).
The inspection of your NATICK facility, which your firm identified as the Complaint Management Center (CMC) for your Enteryx product, revealed inconsistencies with regard to who makes the final MDR decisions. For example, it was observed that not all complaints are reviewed by the CMC for MDR reportability. We observed that your manager for post market compliance in this area sees only those complaints determined to be MDR reportable, and not those determined not to be reportable. Your firm has claimed that there is a review performed by a Medical Director; however, this review is not documented and was not available to our Investigators.
5. Failure to establish and maintain procedures for implementing corrective and preventive action, including requirements for analyzing complaints, as required by 820.100(a)(1).
In MAPLE GOROVE, your firm failed to initiate a corrective and preventive action to correct the recurring problem of late MDR submissions. During this inspection it was noted that a corporate audit in May 2005 documented problems with late MDR reporting. At this time, training was instituted; however, a CAPA was not initiated to correct this serious ongoing problem.
Problems with your corporate CAPA system were identified in the Warning Letters you received last year. We continue to be concerned that the corporate CAPA program currently in place at your facilities is not an effective program to meet the requirements set forth in our regulations.
6. Failure to establish and maintain procedures to address the identification, documentation, evaluation, segregation, disposition and investigation of nonconforming product, as required by 21 CFR 820.90(a).
For example, procedures are still lacking to ensure consistency in the handling and timing in the handling and timing activities from complaint receipt, complaint trending, ship hold, Product Inquiry Report (PIR) initiation, and field action determination, to actual recall. This was seen by the delay in your Enteryx field action at your NATICK facility as well as the failure of your own manufacturing facility to be aware of the field action taking place with the Leveen Needle Electrode in SPENCER.
In addition to serious violations of the QS regulations, the above-stated inspection revealed that your devices are misbranded under section 502(t)(2) of the Act, 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 and 21 CFR Part 803 (Medical Device Reporting [MDR]) and 21 CFR Part 806 (Medical Devices: Reports of Corrections and Removals).
Significant violations include, but are not limited to, the following:
1. Failure of a manufacturer to report, within 30 days of becoming aware of information from any source that reasonably suggests that a device marketed by the manufacturer may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1).
In NATICK, your firm did not submit 5 complaints (#655872, #654048, #657144, #660103, and #655874) for your Enteryx product as MDRs for reports of dysphasia and dilatation.
Also in NATICK, you failed to promptly report to the FDA the results of 4 MDR-reportable complaints that were reported to your firm concerning your devices.
In MAPLE GROVE, you failed to promptly report to the FDA the results of sixty six (66) MDR-reportable complaints that were reported to your fun concerning your devices. The days ranged from 31 days to 366 days late and covered the period January 2004 to July 2005.
2. Failure of a manufacturer to report within 30 days of becoming aware of information from any source that reasonably suggests that a device marketed by the manufacturer has malfunctioned and this device or a similar device would be likely to contribute to a death or serious injury if the malfunction were to recur, as required by 21 CFR 803.50(a)(2).
In SPENCER, you failed to promptly report to the FDA the results of sixteen (16) MDR-reportable complaints that were reported to your firm concerning your devices. The reporting times for all 16 of these events were greater than 40 days (6 were greater than 100 days).
In MAPLE GROVE, you failed to promptly report to the FDA the results of thirty six (36) MDR-reportable complaints that were reported to your firm concerning your devices. All 36 of these events were greater than 30 days.
In NATICK, you failed to promptly report to the FDA the results of eighteen (18) MDR-reportable complaints that were reported to your firm concerning your devices. The time frames ranged from 5 days late to 9 months late.
3. Failure of a manufacturer to submit a written report to FDA of any correction or removal of a device initiated by the manufacturer to reduce a risk to health posed by the device, as required by 21 CFR 806.10(a)(1).
A. PIR #SJC-2005-01-01 was initiated 12/3/2004:
Your recall of the Position Acquisition Module (PAM) as part of the RPM system (including 3 UPNs, all lots) was not reported to FDA, as required by the above-cited regulation. The device is used on patients receiving ablation for arrhythmias. The PAM does not meet IEC 60601-1 General Requirements for Safety of Medical Electrical Equipment. During overheating testing, it was discovered that the [redacted] secondary of the PAM transformer failed short circuit testing, implying the possibility of a fire hazard. The Clinical Assessment for Severity is listed as Critical. The Field Action recommended is to conduct a recall. The recall is classified by Boston Scientific as Class III. This was approved by the FAC Chairperson on 1/24/2005. The equipment has been distributed to both US and OUS consignees.
B. PIR # SJC-2005-03-03 was initiated 2/3/2005:
Your recall of the Signal Acquisition Module (SAM3) as part of the RPM system (including all UPNs starting with M004308300), was not reported to FDA, as required by the above-cited regulation. The device is used on patients receiving ablation for arrhythmias. The SAM3 does not meet IEC 60601-1 General Requirements for Safety of Medical Electrical Equipment. During overheating testing, it was discovered that the secondary of the SAM3 transformer failed short circuit testing, implying the possibility of a fire hazard. The Clinical Assessment for Severity is listed as Critical. The Field Action recommended is to conduct a recall. The recall is classified by Boston Scientific as Class III. This was approved by the FAC Chairperson on 3/14/2005. The equipment has been distributed to both US and OUS consignees.
The FDA's CDRH reviewed the information regarding these two recalls and has determined that they meet the level of a Class II recall.
This letter is not intended to be an all-inclusive list of deficiencies at the facilities inspected. 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 Form FDA-483 issued at the conclusion of each inspection indicate, continued serious underlying problems in your establishment's quality system. You are responsible for investigating and determining the causes of the violations identified by the FDA. You also must promptly initiate permanent corrective and preventive action on your Quality System.
You should know that these serious violations of the law may result in FDA taking regulatory action without further notice to you. These actions include, but are not limited to, seizing your product inventory, obtaining a court injunction against further marketing of the product, or assessing civil money penalties. Also, Federal agencies are informed about the Warning Letters we issue, such as this one, so that they may consider this information when awarding government contracts.
Additionally, no premarket submissions for Class III devices to which the QS/Current Good Manufacturing Practice deficiencies are reasonably related will be cleared or approved 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.
We acknowledge the receipt of your initial letter dated September 23, 2005 and signed by Brian R. Burns, Senior Vice President Global Quality, which was in response to the Form FDA 483 that was issued to your NATICK facility on August 26, 2005. We have also been monitoring your monthly responses to this FDA 483. BSC has indicated a global approach to the systemic problems noted by FDA at a number of your facilities, specifically SPENCER and MAPLE GROVE. We acknowledge the general commitments to certain FDA-483 items that have been made in response to the serious violations. However, your responses continue to be specific spot fixes and have failed to achieve the necessary systemic approach to comprehensively address the violations. This is evidenced by the continuing problems identified above, after you stated in a letter that your firm is moving promptly to correct all the noted deficiencies. The violations included in this Warning Letter and discussed above concern significant deficiencies that warrant your immediate attention to assure that an effective quality system is in place.
It is necessary to take action on this matter now. As discussed in this letter, please contact Karen Archdeacon, Compliance Officer, New England District Office, at the number below to schedule a prompt meeting.
Please direct your response or any questions you may have to Karen Archdeacon, Compliance Officer, Food and Drug Administration, One Montvale Avenue, 4th Floor, Stoneham, Massachusetts 02180. Her telephone number is (781) 596-7707; her fax number is (781)596- 7899.
Gail T. Costello
New England District
Timothy A. Ulatowski
Office of Compliance
Center for Devices and Radiological Health