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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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St Jude Medical, Inc. 17-Mar-05

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

Public Health Service
Food and Drug Administration


466 Fermandez Juncos Avenue
San Juan, Puerto Rico, 00901
Telephone 787-474-9500
FAX: 787-729-9500

March 17, 2005



Daniel J. Starks
St Jude Medical, Inc.
Global Headquarters
One Lillehei Plaza
St. Paul, MN 55117-9983

Dear Mr. Starks:

During a September 27, 2004 through November 9, 2004 inspection of your establishment, St. Jude Medical Puerto Rico, B.V., located at Lot 20 B St. Caguas West Industrial Park, Caguas, PR, our investigators determined that your firm manufactures Angio Sea1™ Vascular Closure Devices which are medical devices (class III) as defined by Section 201(h) [21 U.S.C. 321(h)] of the Federal Food, Drug and Cosmetic Act (the Act).

As described in the Form FDA-483 issued to your firm, the investigators documented significant deficiencies from the Quality System regulation for medical devices as specified in Title 21, Code of Federal Regulations, Part 820. Our review reveals that these are violations that cause the devices to be adulterated within the meaning of Section 501(h) [U.S.C. 351(h)] of the Act in that the methods used in, or the facilities or controls used for manufacturing, packing, storage, or installation are not in conformance with the regulations.

Significant deviations include, but are not limited to, the following:

I. Failure to establish and maintain procedures to control product that does not conform to specifications as required under 21 CFR 820.90(a) . For example;

a. Angio Seal Vascular Closure Device batches [redacted] were found with non-conforming results for the [redacted]. The disposition and release for distribution of these
batches were based on a Reject Material Review (No [redacted]) generated for lot [redacted] for which you also failed to adequately evaluate, investigate, and address the cause of the non-conformance results obtained for the [redacted].

b. The decision to release the Angio Seal Vascular Closure Device batches referenced under item 1.a. was not justified since it was based on passing results for batch [redacted] by means of an unapproved method [redacted]. As indicated, this method is not approved to test the finished product [redacted]. There is also no evidence to demonstrate [redacted] that these batches met the [redacted] prior to being released.

c. The Reject Material Review (RMR) No.[redacted] generated to document the [redacted] results for Angio Seal Vascular Closure Device lot [redacted] indicated that the peel force was not reported for two of the [redacted] samples because the samples had fallen apart while placing the samples in the [redacted]. However, no investigation was conducted to explain a discrepancy in the RMR, which indicates that two non-reportable results were obtained, while the same units presented evidence of heat sealing. In addition, RMR No. [redacted] concludes that lot [redacted] had no values [redacted] for the [redacted] however, the peel test data sheet indicates that a non-conforming value of [redacted] was obtained.

d. Batches [redacted] and [redacted] were released even though they had failed the [redacted] during the finished device testing or the [redacted]. Neither an investigation nor a justification for not conducting a potential root cause analysis was generated.

e. Numerous RMRs failed to follow Procedure No. [redacted] (used for the disposition of Nonconforming Material), in that your firm did not identify the cause(s) for the
non-conforming results obtained. In other reported instances, RMRs failed to record the actions required for disposition. This same procedure, No. [redacted] is further deficient in that it fails to clearly describe the necessary steps to evaluate and conduct non-conformance investigations.

2. Failure to establish and maintain process control procedures that describe any process controls necessary to ensure your product is in conformance to specifications as required under 21 CPR 820.70(a). For example, your firm fails to monitor the polyfoil pouch sealing process even though numerous non-conformances have been obtained.

3. Failure to ensure that only product lots that have passed or are in conformance with the required acceptance activities are distributed as required under 21 CFR 820.86. For example,

a. Angio Seal Vascular Closure Device batches [redacted] and [redacted] were released for distribution even though they had failed to meet [redacted]. [Redacted] of the [redacted] batches were distributed by means of a "Use As Is" disposition even though numerous retests were conducted that resulted in repeated out-of-specification
results of [redacted]. Furthermore, "Use As Is" disposition for lot [redacted] was based on RMR [redacted] generated for a different lot [redacted]. This referenced RMR, documenting [redacted] was not investigated.

b. Out-of-specification results were obtained for the [redacted] conducted to Angio Seal Vascular Closure Device batches [redacted] and [redacted]. However, these batches were given disposition on a "Use As Is" determination based on the rationale that water hydrates collagen collagen than blood and therefore would result in [redacted].

c. Numerous non-conformance results to the [redacted]. These non-conformance prompted many, [redacted], that repeatedly resulted in additional non-conformance results.

The rationale used to explain the out-of-specification results of item 3.b. fails to justify your decision to distribute these batches. Your conclusion that water hydrates quicker than blood raises concerns regarding the validity of other batches tested under the same conditions and found within specification. In addition, water has always been used as the vehicle to perform the [redacted]. Please provide any study you may have available to support your conclusion and explain why your rationale only applies to batches [redacted] and [redacted].

4. Failure to establish and maintain a written procedure addressing the review and disposition process of non-conforming product, along with requiring justification for the use of non-conforming product as required under 21 CFR 820.90(b) . For example,

a. The inspection found that numerous retests were conducted after obtaining nonconformance results for the polyfoil peel force test without having a written procedure in place describing the manner and criteria to be used during the retest.

b. The records reviewed lack the justification or critecia used to sort the units of Angio Seal Vascular Closure Device from lot [redacted] (andlor other batches), into poor and good seal groups (or "Good , "OK , "No Seal" and "Poor Seal"). Furthermore, there are no procedures describing the criteria used to sort units into an acceptable or reject group.

c. Lots that failed the polyfoil test were retested using different sample sizes and test methods. For example;

i . Lot [redacted] was retested [redacted] times, using approximately [redacted] samples for the [redacted], followed by Ct samples tested using a different method [redacted]

ii . Lot [redacted] was retested using [redacted] samples for the [redacted] followed by [redacted] samples using the [redacted]

iii. Lot [redacted] was retested with [redacted] samples using the [redacted] for [redacted]

iv. Lots [redacted] was retested using [redacted] additional samples for the [redacted]

d. Lots [redacted] and [redacted] were all non-conforming lots with the same failure mode [redacted] but the dispositions of the lots were based on different justifications and rationale.

5. Failure to establish and maintain procedures for implementing corrective and preventive actions as required by 21 CFR 820.100 (a), and failure to document all
activities as required under 21 CFR 820.100 (b)
For example;

a. A CAPA file including an evaluation of the significance of the high deployment force test results for batches [redacted] and [redacted] was not generated as required.

b. Your Reject Material Review No.[redacted], makes reference to CAPA No. [redacted] opened at your Minnetonka facility, due to multiple lots with results of [redacted]
during final lot release testing. This referenced CAPA had no due date, or indication that a root cause analysis had been conducted involving the batches manufactured at your Puerto Rico facility.

c. The items identified as and preventive actions under CAPA are investigational issues and do not meet the requirements for corrective and preventive actions under 21 820.100(a). Examples are as follows: investigate correcting high deployment forces, with the study of varying collagen properties, investigate correcting high deployment with modifications to the Angio-Seal device, changes to component over time, and investigate correlations in [redacted] with [redacted].

d. Your CAPA Procedure No.[redacted] does not clearly specify the criteria or circumstances necessary to trigger CAPA investigation and related corrective and
preventive actions.

e. Your CAPA procedure [redacted] also lacks provisions for performing a risk analysis during investigations of quality problems.

f. The CAPA Investigations were found lacking assigned due dates for completion.

g. CAPA investigations were not opened in a timely manner or when necessary.

Please provide in your response specific corrective actions to ensure that any CAPA opened at your SJM-Minnetonka facility, affecting products manufactured at St. Jude Medical Puerto Rico, are promptly referred to your Puerto Rico plant for appropriate evaluation.

6. Failure to establish and maintain corrective and preventive procedures to assure that all sources of quality data are analyzed to identify existing and potential causes of nonconforming product and other quality problems as required by 21 CFR 820.100 (a)(1).

For example:

a. Complaint data is not routinely analyzed for trends of potential quality problems to determine if a formal investigation and/or CAPA is necessary.

b. Fifteen complaints related to Angio Seal-STS platform manufactured between February and March 2004, reporting [redacted] causing the slit in the carrier to separate and [redacted] during the medical procedure" were not thoroughly investigated to identify the probable root cause.

c. An investigation or formal study addressing the potential cause for the [redacted] related to the Angio Seal STS platform was not available.

We have received your response letter dated December 7, 2004 replying to the FDA 483 issued on November 09, 2004, and amended on December 17, 2004, and find it to be deficient for the following reasons:

There is no indication of action taken against any batches of Angio-Seal Vascular Closure Device distributed even though numerous retests were conducted and confirmed out-ofspecification results.

The iustification provided for item lA of the FDA-483 is inadequate in that the test [redacted] .i used to approve the disposition of lots [redacted] and [redacted] is not the release test method approved for the post-sterilization test. Please include in your response any written communication received from FDA-ODE confirming the use of an alternate method when non-conformance results are obtained and to approve the disposition of the affected batches. Also include an explanation for releasing those batches in which water was used instead of blood during the force deployment test and the rational for finding them in-conformance with the specifications.

Your response for item 1D of the FDA-483m does not justify the decision to not conduct an investigation.

  • Your response to item 2A of the FDA-483 fails to include a written procedure as cited under this item. Please provide in your response the specific guidelines defining and explaining how and when a retest will be conducted. The specific steps should be defined.

  • Include with your response copies of the modified procedure(s) modified as mentioned under your written response to FDA-483 item 3C. Also include a copy of the final approved procedures mentioned as being rewritten in your response to FDA-483 items #4 through #8.

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 FDA and must promptly initiate permanent corrective and preventive actions to address these problems.

It is necessary for you to take action on this matter immediately . 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.

In addition, no requests for Certificates to Foreign Governments will be approved until the violations related to the subject devices have been corrected. Federal agencies are also 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.

Please let this office know in writing, within fifteen (15) working days from the date you received this letter, what steps you are taking to correct the problem, including steps being taken to identify and correct any underlying system problems to assure that similar violations will not happen again. If you need more time let this office know why and when you expect to complete your corrections.

Your reply should be sent to the Food & Drug Administration, San Juan District Office, 466 Ferndndez Juncos Ave., San Juan, PR 00901-3223, Attention: Carmelo Rosa, Compliance Officer.



Donald J. Voeller
District Director
San Juan District