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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Tyco Healthcare Group 27-Sep-05

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

Public Health Service
Food and Drug Administration
  San Francisco District
1431 Harbor Bay Parkway
Alameda, CA 94502-7070
Telephone: 510/'330-6700


September 27, 2005

FEDERAL EXPRESS

WARNING LETTER

Richard J. Meelia
CEO/President
Tyco Healthcare Group
15 Hamshire Street
Mansfield, MA 02048

Dear Richard Meelia:

During an inspection of your firm located in 4280 Hacienda Drive, Pleasanton, California, on January 18, 2005, through March 24, 2005, our investigators determined that your firm engages in manufacturing operations for endotracheal/tracheostomy tubes and accessories, temperature monitoring and disposables, infusers, irrigators, respiratory support products, patient warming and blood/fluid warming disposables, oximetry sensors, manual resuscitators and other respiratory supplies, pulse oximetry monitors, ventilators and accessories, sleep apnea therapy products, filters, and heat and moisture exchange devices (HMEs). These products are devices within the meaning of section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 321(h)).

This inspection revealed that these devices appear to be 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. Significant violations include, but are not limited to, the following:

1. Failure to establish, maintain, and implement procedures for validating the device design, as required by 21 CFR 82030(g). Examples of your failure to adequately implement these requirements include the following:

a. The design validations for the FIexTra, PERC, DCT, PFEN, LPC, and LPCS tracheostomy tubes do not use initial production units from the facilities where they are or will be manufactured. Nor was there scientific evidence proving that the devices used for the design validation were equivalent to initial production units. In addition, there was no assessment of the production environment conditions on the performance of the cuff.

b. The characteristics and specifications for the FlexTra tracheostomy cuff were transferred from the DCT and PERC tracheostomy tubes. You state that the FlexTra cuff design is the same as the DCT and PERC and that the only differences are the sizes. However, you did not document a scientific justification that the cuff characteristics are equivalent between the FlexTra, DCT, and PERC tracheostomy tubes.

c. Your firm's hazard analysis failed to identify calibrant solution contamination and microbial contamination of the CapnoProbe SLS1 sensors during the transfer of manufacturing operations from [redacted] to your firm's T'ijuana, Mexico facility. There was no documentation to assure that these hazards were mitigated.

d. Scientific evidence was not documented to justify changes made to the acceptance criteria specifications for the FlexTra tracheostomy tubes. The Specification, Product Assurance Plan, FlexTra Flexible tracheostomy Tube, Drawing Number [redacted], ,Appendix [redacted] Verification and Validation test Plan and Report describes the performance testing to be conducted. Rev. A of this document specifies that the acceptance criteria are to be "[e]qual to or better than XLT." However, Revisions B and B/1 of this document changed the acceptance criteria to quantitative values but did not include a justification for these changes.

2. Failure to establish and maintain design input procedures that include a mechanism for addressing incomplete, ambiguous, or conflicting requirements, as required by 21 CFR 820.30(c). An example of your failure to adequately implement this requirement includes the following:

ASTM F1666-95, Standard Specification for Adult Tracheostomy Tubes, is referenced in the various Shiley FlexTra Tracheostomy Tube design input requirements for the [redacted] cannula hub tensile resistance, [redacted] cannula tip strength, and [redacted] cannula-to-head base tensile strength. However, ASTM F1666 does not address these input requirements, nor are they addressed elsewhere in your design input procedures.

3. Failure to establish, maintain, and implement procedures for receiving, reviewing, and evaluating complaints, as required by 21 CFR 820.198(a).

For example, the following service reports received by the firm and classified as complaints were not evaluated to determine if the complaints :represented events which were required to be reported to FDA as MDRs:

o Request Number 637967-001, dated 04/29/03
o Request Number 627295-001, dated O1/27/03
o Request Number 625818-001, dated O1/14103
o Request Number 627228-001, dated O1/27103
o Request Number 628341-001, dated 02/05103
o Request Number 638330-001, dated 05/O1/03
o Request Number 648633-001, dated 07/28103
o Request Number 653155-001, dated 09/03/03

4. Failure to review and evaluate all complaints to determine whether an investigation is necessary and, if applicable, to maintain a record that includes the reason no investigation was made, as required by 21 CFR 820.198(b).

For example, the following complaint records did not specify the reason/justification for why no investigation was necessary:

o RP200411-09171, dated 11/08/04
o RP200412-13161, dated 12/28/04
o RP200407-08502, dated 07/22/04
o RP200407-00171, dated 07/01/04
o RP200310-03181, dated 10/06/03
o RP200310-02562, dated 1O/03/03

5. Failure to establish and maintain procedures for implementing corrective and preventive actions that include requirements for analyzing appropriate sources of quality data, as required by 21 CFR 820.100(a)(1). An example of your failure to adequately implement this requirement includes the following:

Management review action items are not fed into the corrective and preventive action system.

6. Failure to establish, maintain, and implement procedures to identify the actions needed to correct and prevent recurrence of nonconforrning product and other quality problems, as required by 21 CFR 820.100(a)(3). These actions must be documented as required by 21 CFR 820.100(b).

For example, the CAPA records for the Shiley Tracheosoft XLT tracheostomy tubes, CapnoProbe sensors, FIexTra tracheostomy tubes, 700 series ventilators, and pulse oximeters do not identify that recalls were initiated as corrective actions.

7. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50 . An example of your failure to adequately implement this requirement includes the following:

The firm's October 2001 and 2004 vendor qualifications failed to adequately evaluate known failure modes of the speaker component used in the NPB-290, NPB-295, N-395, and N-595 pulse oximeters.

8. Failure to maintain distribution records which include or refer to the location of any control number used, as required by 21 CFR 820.160(b)(4).

For example, your distribution records for the FlexTra tracheostomy tube do not contain the control numbers for these devices. Control numbers identifying each unit, lot, or batch are required for finished devices that are intended for surgical implant into the body or to support or sustain life and whose failure to perform when properly used in accordance with instructions for use provided in the labeling can be reasonably expected to result in a significant injury to the user 21 CFR 820.65. These control numbers must be recorded in your distribution records along with the any control numbers voluntarily used.

9. Failure to establish, maintain, and implement procedures for identifying valid statistical techniques required for establishing, controlling, and verifying the acceptability of process capability and product characteristics, as required by 21 CFR 820.250(a).

For example, your firm does not have a procedure to support the appropriateness of the statistical techniques used for the following:

o The sample size of "2 each of sizes 6, 8, and 10-6 samples" for the Quality Assurance Test Procedure, QAT# 000312, dated 04-03-03, for the FlexTra outer cannula tip flexture strength test.
o Changes in the sample sizes used to verify and validate the reliability and safety of the FlexTra tracheostomy tubes in the Product Assurance Plan and Report for FlexTra Flexible Tracheostomy Tube, Drawing Number [redacted] dated 12/19/02, Appendix A - Verification and Validation Test Plan and Report. For example, sample sizes were changed under Revisions B and B/1 for Test 2, Locking Torque; Test 3, Tensile resistance to pull out inner cannula hub; Test 8, Tensile strength - outer cannula to head base; Test 10, Tensile strength - inflation line to outer cannula. However, no documented rationale exists to support the changes to the sample sizes for this test.

10. Management with executive responsibility has not assured that quality objectives are implemented, as required by 21 CFR 820.20. For example:

a. The firm's organizational structure documented in the Quality Manual and Organizational Charts does not give sign off authority to the Vice President of Regulatory Affairs, Quality Assurance, and Clinical Affairs (RA/QA/CA) on quality matters as defined in the position's job description, i.e., procedural changes, development of quality policies.

b. The premarket notification submission for the FlexTra tracheostomy tube was not reviewed for accuracy before submission to FDA. Discrepancies were observed between versions of electronic test records maintained in the shared drive, back-up drive, paper copies of the DHF, and records submitted to the Agency.

c. Various Quality System procedures have not been reviewed and/or updated.

d. Two databases are used to handle complaints, with the result that management is only made aware of some complaints received.

11. Failure to conduct quality audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. An example of your failure to conduct adequate quality audits includes the following:

Your firm's Quality System Audits procedure, PIN: NP060096, Rev. H/l, requires that Quality System Audits be performed by trained auditors who have no direct responsibility in the areas being audited. However, the internal audit team members have remained consistent for over three years and your firm's organizational charts indicate that the auditors are members of the various departments for which they have direct responsibility.

The above stated 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 to furnish material or information as required under section 519 of the Act and regulations implementing that section at Title 21 Code of Federal Regulations (21 CFR), Part 803 - Medical Device Reporting. Significant violations include, but are not limited to:

You failed to submit MDR reports 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 injury in accordance with 21 CFR 803.50(a)(l) or has malfunctioned and would be likely to) cause or contribute to a death or serious injury if the malfunction were to recur, as required in 21 CFR 803.50(a)(2).

For example, complaints involving hub separation on tracheostomy tubes, alarm failures of pulse oximetry meters, and tracheostomy tube cuff leaks were not reported.

You also failed to develop, maintain, and implement written MDR procedures, as required in 21 CFR 803.17. An example of your failure to adequately implement this requirement follows:

You do not have written procedures to handle medical device reportable events for tracheostomy tubes, endotracheal tubes, temperature monitoring systems, patient warming and blood/fluid warming disposables. In addition, procedures for other devices fail to provide for a standardized review process for determining when an event meets the criteria for reporting and fail to include documentation and recordkeeping requirements for all information that was evaluated to determine if an event was reportable.

This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations 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 underlying problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.

We received a response from David Sell, President, Nellcor, dated April 22, 2005, and met with representatives of Nellcor, including Mr. Sell, and Tyco Healthcare, including Tom Gonzalez, Vice President, Quality Assurance and Regulatory Affairs, on May 24, 2005 concerning our investigators' observations noted on the FDA 483. We have reviewed your response to the above items and have concluded that it is inadequate because the specific documentation to demonstrate the implementation of your corrective actions has not been provided. Please submit copies of your revised procedures and documents, re-organizational charts, auditing plans and findings, and re-training records, and for our review. Your stated corrective actions include, but are not limited to, the following:

1. A revised risk assessment (NP060487) and FMEA (NP047950) procedures that will require the design review of the potential impact of the production environment on the performance of devices. In addition, please explain how your hazard/risk analysis activities will be validated and linked to design review and revise the relevant procedures accordingly.

2. Updated design outputs and performance requirements of the cuffs for the Shiley tracheostomy products that include specific acceptance criteria in accordance with your Design Control procedure (NP06020) and a revised Design Control procedure that clearly requires measurable design verification and validation parameters and acceptance criteria.

3. A revised protocol review procedure that requires quantitative acceptance criteria for verification and validation testing.

4. Revised service, complaint, and MDR procedures to ensure that service requests that meet the definition of a complaint under 21 CFR 820.198 or MDR reportable event under 21 CFR 803.3 will be processed in a uniform and timely fashion. These procedures are intended to provide a standardized review process for determining when an event meets the criteria for reporting.

5. A revised Management Review procedure that requires management review of action items to be entered into your CAPA system.

6. A new division level procedure for supplier qualification that will include consideration of known failure modes for purchased components. In addition, please submit a copy of the January 2005 technical report, "Destructive Physical Analysis of [redacted] Micro-Speakers" that qualified the speakers used in the NPB-290, NPB-295, N-395, and N-595 pulse oximeters for our review.

7. A revised internal audit policy and procedure.

8. A revised documentation hierarchy to standardize policies and procedures.

9. A revised Quality Manual and organizational charts to more clearly indicate the link between executive management and your firm's business units. This information should include the job descriptions of the corporate sterilization/microbiology group and Director of Product Monitoring.

10. A summary of your review of all market withdrawals and recalls and associated CAPA records for the past two years.

11. Auditing of key processes that have been introduced to the manufacturing facility, including an assessment of whether the manufacturing environmental control and process validation address critical aspects of the product design.

12. Auditing by your firm's third-party consultants of existing DHFs to ensure that acceptance criteria for design output are in place, that specifications have been developed in accordance with your revised design control procedures, and that existing DHRs include verification and validation activities as they pertain to acceptance criteria. This audit should further include a review of verification and validation activities, to ensure that appropriate standards are referenced, and to ensure the appropriateness of sample sizes and to confirm that sample sizes have statistical significance.

13. A third-party audit plan to review vendor qualifications.

14. Revised design control training to address risk analysis, FMEA, design output, design verification and validation, and design transfer activities.

15. Employee training on your new electronic complaint tracking system and procedures.

16. A corporate training program in Design for Six Sigma (DFSS) to provide tools for improving design methodology tools which includes statistics for sample size justification.

17. Revised complaint/MDR procedures and results of your retrospective complaint/MDR audit, including the procedures for conducting the audit.

18. Revised recall procedure and evidence of employee retraining.

In addition, please provide the following:

i. Revised CAPA records for the Shiley Tracheosoft XLT tracheostomy tubes, CapnoProbe sensors, FlexTra tracheostomy tubes, 700 series ventilators, and pulse oximeters that identify the market withdrawal corrective actions taken.

ii. Your plan to redesign the FlexTra and XLT tracheostomy tube products and an estimated timeframe for the submission of 510(k) Notifications for these redesigned products.

You should take prompt action to correct the deviations described above. Failure to promptly correct these deviations may result in regulatory action, which may include detaining your FlexTra, PERC, DCT, PFEN, LPC, and LPCS tracheostomy tube products without physical examination upon entry into the United States until the corrections are completed. Section 801(a) of the Act (21 USC 381(a)).

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 violations, or similar violations, from occurring again. Include all documentation of the corrective action you have taken. If you plan to make any corrections in the future, include those plans with your response to this letter as well. If the documentation is not in English, please provide a translation to facilitate our review.

Your response should be sent to the Food and Drug Administration, San Francisco District, 1431 Harbor Bay Parkway, Alameda, CA 94502, to the attention of Russell A. Campbell, Compliance Officer.

If you need help in understanding the contents of this letter, please contact Mr. Campbell at the above address or at (510) 337-6861.

Sincerely yours,

/S/


Barbara J. Cassens
District Director