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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Boston Scientific Corporation 10-Aug-05

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

Public Health Service
Food and Drug Administration


New England District
One Montvale Avenue
Stoneham, MA 02180
(781) 596-7700
FAX: (781) 596-7896




August 10, 2005

Mr. James Tobin
Boston Scientific Corporation
One Boston Scientific Place
Natick, MA 01760-1537

Dear Mr. Tobin:

We are writing to you because on March 28 through May 20, 2005, the Food and Drug Administration (FDA) conducted an inspection of your Boston Scientific Corporation, (BSC) Quincy, Massachusetts facility which revealed serious regulatory problems involving your medical devices, including the implantable Vaxcel Low Profile Infusion Ports, Taxus paclitaxel drug eluting stents, and Symmetry balloon dilatation catheters.

Under a United States law, the Federal Food, Drug and Cosmetic Act, (the Act) these products are considered to be medical devices because they are used to diagnose or treat a medical condition. Moreover, your manufacturing activities, including labeling, holding and distributing, make you a manufacturer under the law. The inspection found 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, (21 CFR), Part 820. Significant deviations include, but are not limited to, the following:

1. Failure to identify the acceptance status of product throughout manufacturing, packaging, labeling, and servicing of the product to ensure that only product which has passed the required acceptance activities is distributed as required by 21 CFR 820.86. For example, on a number of occasions, your firm shipped medical devices that were not considered acceptable for release.

a. On January 20 and 21, 2005, your firm shipped [redacted] units of Taxus Express 2, Monorail, Paclitaxel-Eluting Coronary Stent System, [redacted], to 5 separate hospitals. All of the [redacted] units of this particular batch were part of a coated stent [redacted] that had failed the kinetic drug release (KDR) test and were later scrapped. All of these [redacted] units were placed in quarantine on October 27, 2004. However, on January 20 and 21, 2005, a total of 8 units from this batch were released by your facility and were distributed to hospitals.

b. On at least 3 separate occasions - September 21, 2004, December 14, 2004 and February 15, 2005, your firm distributed 5 units of the Vaxcel Low Profile Infusion Valved Ports to hospitals for later implantation into patients. Prior to these dates, BSC placed all of the Vaxcel Low Profile valved ports on shipping hold on August 25, 2004 because of one complaint of port separation. On the 3 dates noted above, these products were in quarantine and should not have been allowed to be distributed to hospitals.

c. In September 2004, your firm released [redacted] batches of Symmetry balloon dilatation catheters into finished goods inventory without a final release disposition. At least [redacted] units of these Symmetry balloon dilatation catheters were further distributed to hospitals. These [redacted] batches were part of a shipping hold instituted by BSC Galway on August 23, 2004 due to a problem seen with "bond degradation". During our inspection at your facility, you had no information or documents to establish that a final release from your BSC Galway manufacturing facility was provided for a final disposition of these [redacted] batches that had already been distributed to customers.

In your response dated June 20, 2005, you state that you have suspended the shipment of medical devices to Sales Representatives for use as "Trunk Stock". Please let us know what date this went into effect. Please also notify our office when or if you plan to resume the Sales Representative Trunk Stock Program.

In your response you provided us a copy of a release form from Galway, dated June 3. 2005 that provided for the release of the [redacted] batches [redacted] of the Symmetry balloon dilatation catheters into finished goods. This final release is at least eight months after the units had been distributed. Your response, however, fails to describe what corrective actions BSC plans for product that was released prior to this release and are currently in the field.

2. Failure to establish adequate management controls to ensure that an effective quality system has been established and maintained as required by 21 CFR 820.20. For example, BSC has failed to implement procedures to assure that only devices approved for release are distributed.

In your response dated June 20, 2005, you have indicated that you are committed to making a number of corrective actions to improve your quality system.

However, your response does not identify how and when you plan to implement significant, broad-based corrective actions, nor does it provide sufficient evidence to establish that you have made real changes to your current quality system to ensure control over the release and distribution of your devices.

3. Failure to analyze processes, work operations and other sources of quality data to identify existing and potential causes of non-conforming product as required by 21 CFR 820.100(a)(1). For example, we observed the release and actual shipment of [redacted] non-conforming medical devices, specifically [redacted] units of the Taxus Express 2, Monorail, Paclitaxel-Eluting Coronary Stent System to 5 separate hospitals on January 20 and 21, 2005. These devices had failed the kinetic drug release test results and were part of a "shipping hold". Through a failure of your quality system, two employees were able to override your computer systern, removing the "S-block" to release these devices electronically. These devices were physically removed from a quarantined area and subsequently shipped to 5 separate hospitals. As part of your review of this serious event, you initiated a Product Inquiry Report, (PIR) 2005-01-01. The medical/clinical assessment of this event your firm indicated that the probability of detecting this event was "high". Yet the rationale for this detection level stated, "While visual control through the implanting physician will not allow any detection of the occurrence (these stents are visually indistinguishable from the stents within spec), the established KDR controls will continue to provide a high chance to detect outliers before distribution". We note that this assessment went through your review and approval process. You listed a detection level as "high", however, your own rationale states that the actual failed stents are visually indistinguishable from stents within specification. Moreover, you stated that the KDR controls provide a high chance to detect outliers before distribution ; however, the [redacted] units actually shipped had failed KDR testing.

Your response letter dated June 20, 2005, stated the P1R was updated to reflect the change in detection level from "high " to "catastrophic".

Although you have made that change, serious events such as the one described above, require a thorough review of the facts that precipitated the actual shipment of this adulterated class III medical device. These events indicate a complete failure of your quality system, and are significant and serious.

4. Failure to document all activities performed in regards to your corrective and preventive activities, including the investigations of causes of nonconformities, and the actions needed to correct or prevent recurrence of non conforming product and other quality problems, as required by 21 CFR 820.100(b). During our inspection, we reviewed several BSC CAPAs. This review indicated that your CAPAs fail to include all the necessary information to describe the incident and / or the non conforming condition.

For example, BSC CAR-05-004 which involved the shipment of [redacted] units of failed Taxus Express 2, Monorail, Paclitaxel-Eluting Coronary Stent System, to 5 separate hospitals. This CA-PA only states, "Taxus Express 2 product part number H7493897012250, Batch [redacted] was removed by an operator from a QA quarantined location for shipping. The skid containing these units was labeled 'Pending KDR Test Results' and was also `S' blocked in SAP. A second operator performed an SAP transaction removing the `S' block status. This resulted in the units to ship to customers. " The CAPA did not include the dates of these serious occurrences, the employees involved, or the number of instances that product was actually either removed from quarantine of overridden in the computer system (SAP). The CAPA also did not list the number of units that were actually shipped, or the number of hospitals that actually received non conforming product. We learned through interviews with employees, that there were actually 5 separate removal actions of Taxus product from the quarantined area. On January 12, 2005 [redacted] separate batches of Taxus product were removed from the quarantined area. These were caught by an employee; however, a CAPA was not generated for the incident. Actual shipment of the [redacted] units occurred on January 20 and 21, 2005 when it was realized there was a 5th removal of Taxus from quarantine. The CAPA for this instance was initiated on January 27, 2005.

A serious event such as the one described above, requires a thorough investigation into the activities that precipitated the actual shipment of adulterated Taxus product. Without a thorough investigation into these events, it is difficult to implement an adequate corrective or preventive action that is required by our regulations.

We note in your response letter dated June 20, 2005, that you have supplemented information to the above CAPA and consider the remedial action to be complete and closed. We are concerned that you have not taken adequate action to prevent this type of serious failure from recurring.

5. Failure to establish and maintain an adequate corrective and preventive action procedure which ensures identification of actions needed to correct and prevent the recurrence of nonconforming product and other quality problems, as required by 21 CFR 820.1 00(a)(3). Your CAPA system has failed to identify the necessary actions to correct and prevent the continued distribution of nonconforming product.

For example, we noted that CAPA 04-125 was initiated on November 2, 2004 to address the release of [redacted] batches of Symmetry balloon dilatation catheters into finished goods inventory. The only preventive action taken as the result of this CAPA was to "Update procedure S801280-00". This CAPA was closed on February 15, 2005 with a notation that the CAPA plan was effective. This CAPA did not identify any corrective action for the [redacted] units that were released into finished good without proper authorization. During our inspection, you had no information or documents to establish that a final release from your BSC Galway manufacturing facility was provided for a final disposition of these [redacted] batches that had already been distributed to customers.

6. Failure to document changes in your required records to include a description of the change, signature of the approving official and an approval date, as required by 21 CFR 820.40(b). For example, during our inspection, the FDA investigators reviewed a multitude of BSC records that are required to be kept under the QS regulations, including, but not limited to your PIRs, CAPAs and training records. Many of these important and required records, although appearing to be original documents, had pages with different signatures, pages and dates. We also observed changes being made to documents without any initials, dates or explanations.

Further, your Vaxcel Low Profile Ports are misbranded under section 502(t)(2) of the Act, 21 U.S.C.352(t)(2), in that there was a failure or refusal to furnish material or information required by or under section 519 of the Act, 21 U.S.C. 360i, respecting the device. You failed to report to FDA any correction or removal of a device to reduce a risk to health within 10 working days of initiating the correction or removal, as required by the correction and removal regulations (21 CFR part 806), promulgated under section 519(f)(1) of the Act, 21 U.S.C.360i(f)(1). For example:

On August 25, 2004, your firm implemented a remedial action, specifically a shipping hold of all your Vaxcel low profile valved ports. This was in response to one complaint of port separation. A telephone call on February 25, 2005, with FDA's New England and New York office was the first notification to the FDA that Boston Scientific was conducting a voluntary recall of the Vaxcel low profile valved port due to port separation. However, through our investigation into this voluntary recall, we have determined that your sales representatives, on at least one occasion after the shipping hold was initiated, removed Vaxcel low profile valved ports from a hospital prior to your recall action. On November 22, 2004, a Boston Scientific sales representative removed five units of the Vaxcel low profile valved port from [redacted] and indicated that he discarded the devices in the trash. This occurred following the hospital's complaint of port separation of the Vaxcel Low Profile valved port on November 16, 2004. Our investigation revealed that BSC replaced the Vaxcel low profile valved ports with 5 of your BSC titanium ports. The FDA was not notified of this product correction/removal within the required 10 days.

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 Form FDA-483 issued at the conclusion of the inspection may be symptomatic of 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. 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 III devices to which the Quality System/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 a letter, dated June 20, 2005 and signed by Elizabeth V. Carleo, Director of Quality Assurance and Brian R. Burns, Senior Vice President Global Quality, which responded to the form FDA 483 that was issued to your facility on May 20, 2005. We note that your response fails to address specific system wide corrective actions that are necessary to bring your facility into compliance. We have included our comments to the response in this letter. 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.

You may wish to contact the Recall Coordinator, Susan Liner, in FDA's New England District Office at 781-596-7750 to discuss any violative product currently in commercial distribution. It is necessary to take action on this matter now. Please let this office know in writing what steps you have taken to correct the noted problems within fifteen (15) working days from the date you received this letter. We also ask that you explain how you plan to prevent these problems from happening again. If you need more time, let us know why and when you expect to complete your correction. 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; FAX No. 781-596-7899.

Sincerely yours,


Mark C. Lookabaugh
Acting District Director
New England District