| Public Health Service Food and Drug Administration |
Detroit District |
Department of Health and Human ServicesWARNING LETTER
2011-DET-10
VIA UPS
June 30, 2011
Louis A. Serafin, Jr., MD
President and Owner
Signal Medical Corporation
400 Pyramid Drive
Marysville, Michigan 48040
Dear Dr. Serafin:
During an inspection of your firm located in Marysville, Michigan on March 17, 2011 through April 15, 2011, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufacturers the Symmetric Total Knee System, Unicompartmental Knee System, Ceramic Head, Cancellous Bone Screw, and Microseal Acetabular System. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.
This inspection revealed that these devices are 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. We received a response from Cheryl Warsinske, Engineering and Quality Manager, dated May 5, 2011, concerning our investigators observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to establish and maintain procedures that define the responsibility for review and the authority of the disposition of nonconforming product, as required by 21 CFR 820.90(b)(1). For example: According to the QOP -83-01, Control of Nonconforming Product, effective date August 6, 2009, section 3.1, states justification for use of nonconforming product and the title and signature of the manager authorizing the use are documented in the Disposition block of the Product Nonconformity Report form. Your firm failed to follow the standard operating procedures, in that, there was a failure to document the justification for use of nonconforming product during in-process first article checks and final product testing, and documentation of the disposition on the Product Nonconformity Report in 12 out of 70 device history records reviewed. Examples include: Device 6 x 25 Ultra Tibial Insert, work order (b)(4), Serial number (b) (4); Device 6 x 20 Ultra Tibial Insert, work order (b)(4) Serial number (b) (4); and Microseal Anatomic (10°) Liner 32 x 76 x 10, work order (b)(4) and Serial number (b) (4). All had out of tolerance results but were released for distribution.
The response dated May 5, 2011 is not adequate. Your firm did not provide documented evidence that the 510(k) was originally submitted using the (b)(4) tolerances; and the rationale as to why this tolerance is acceptable to use when the engineering prints have a tolerance of (b)(4). The update to the Control of Non-conforming Procedure, QOP-83-01 is an action item. There is no explanation of the updates to be made.
2. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a).
For example:
a. Your firm did not adequately verify the effectiveness of Corrective/Preventive Action Request #69 opened on November 2, 2010. The nonconforming condition listed was the surface profile was not measured on seven (7) knees and the surface profile box was signed off as N/A by the Quality Manager at final release. One of the associated corrective/preventive actions was to “…retrain the quality technician on the (b)(4) surface profile process”. Our investigators found that not all Quality Technicians were trained to operate the (b)(4) and the order of operations for the (b)(4) surface profile process. Also, your firm reviewed work orders processed prior to the change, but did not evaluate work orders, in-process testing or any other criteria to verify the effectiveness of the implemented corrective and preventive action.
b. Corrective/Preventive Action Request #070 opened on November 14, 2010 states “The articulating surface on 5 tibial inserts did not clean up properly during (b)(4)”. Tibial Inserts parts involved sizes: 5 x 14 Ultra Tibial Insert, 5 x 25 Ultra Tibial Insert, and 5 x 35 Tibial Insert. The corrective/preventive action was to: (b)(4). Your firm failed to address the action(s) needed to correct and prevent recurrence of nonconforming Ultra Tibial Inserts with thickness of 14 mm.
The adequacy of your firm’s response dated May 5, 2011, cannot be determined at this time. The response references actions and projected completion dates but there was not any documented evidence submitted for review.
3. Failure to validate a process whose results cannot be fully verified by subsequent inspection and test, and approve the validation according to established procedures, as required by 21 CFR 820.75(a).
For example:
a. Your firm did not have any documentation that the (b)(4) was installed correctly.
b. Your packaging validation does not include all products packaged at your firm, such as, the Microseal (Augmented, Stable, Anatomic) Liner and Cancellous Bone Screws.
c. Your firm did not challenge all process parameters for the blister sealer (with attached thermocouple). The packaging validation lists the temperature of the blister seal machine at (b)(4). However, the validation does not document the temperature readings of the thermocouple used to verify the temperature of the blister sealer.
The adequacy of your firm’s response dated May 5, 2011, cannot be determined at this time. Your firm has included only projected dates of completion of the validation. There was not any documented evidence to review.
4. Failure to establish and maintain adequate procedures to control all documents, as required by 21 CFR 820.40. For example: Your firm does not have approved device master records for the Cancellous Bone Screws, Microseal (Augmented, Stable, Anatomic) Liners, and Ceramic Heads. The QOP-42-02 Device Master Record, effective date October 29, 2010, Revision F, states in Section 1.1 that DMR documents are established and controlled documents following the same rules that generally apply to all controlled documents. QOP-42-01, Control of Documents, effective date October 29, 2010 states under section 3.2 that the responsibility to review, and issue the document always rests with Engineering or Quality. The records that comprise the device master records for the Cancellous Bone Screws, Microseal (Augmented, Stable, Anatomic) Liners, and Ceramic Heads were maintained on your firm’s computer system and have not been approved by the Engineering and Quality Manager.
The response dated May 5, 2011 is not adequate. There is no evidence submitted for the completed Microseal Liner and Ceramic Head device master records (DMR) and only a projected date of completion for the DMR for the Cancellous Bone Screws. The response also does not address how this process will be handled in the future so products will not be manufactured without approved DMRs.
5. Failure to establish and maintain schedules for the adjustment, cleaning and other maintenance of equipment to ensure that manufacturing specifications are met, as required by 820.70(g)(1). For example, maintenance logs lacked initials of the individual performing maintenance and/or the checkmark for when the maintenance was completed as per the instructions on Form 20-1B.
The response dated May 5, 2011 is not adequate. There was no documented evidence to review. Updates to procedure and maintenance sheets are planned actions but there is no explanation as to the changes that will be made.
6. Failure to establish and maintain adequate procedures for quality audits and conduct such 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. For example, the audit of the Information Resources on July 16, 2010 was conducted by your Engineering and Quality Manager who is directory responsible for document control at your firm. The QOP-82-02, Internal Quality Audits, effective date August 31, 2009, Revision B, states in section 2.1 that personnel assigned to carry out internal audits are independent of those having direct responsibility for the audited activity.
The adequacy of your firm’s response dated May 5, 2011, cannot be determined at this time. The response references projected dates for the new hires training and adjustments to the internal audit schedule.
7. Failure to establish and maintain adequate procedures to ensure the device history records (DHR’s) for each batch, lot or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record (DMR) and the requirements of this part, as required by 21 CFR 820.184. For example, work order #(b)(4) for 26x48x20 Microseal Augmented (20°) Liner did not contain sterilization records for serial numbers (b)(4) and (b)(4) and Work order # (b)(4) for 22x38 Microseal Stable Liner did not contain sterilization documentation for serial number (b)(4) as one of the devices sterilized during load (b)(4)
Your response, dated May 5, 2011, will be evaluated during the next inspection.
8. Failure to adequately develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, as required by 820.70(a). For example, your firm has not developed written procedures for the (b)(4) and turning (e.g. set-up sheets) for all parts of the Symmetric Total Knee System to include the Tibial Insert and Femoral Component; (b)(4) and turning of the Microseal (Stable, Anatomic, Augmented) Liner; and the turning of the Ceramic Heads.
The adequacy of your firm’s response dated May 5, 2011, cannot be determined at this time. The response references projected dates for the validation and approval of the set-up sheets; and a plan for completing the remainder of set-up sheets. The response does not address how this can be prevented in the future. The response also does not address if there is any manufacturing of these products while your firm is in the process of completing the validation and approval of the set-up sheets for the parts manufactured.
9. Failure to evaluate whether there was any adverse effect on the device’s quality when specific directions and limits for accuracy and precision are not met, as required by 21 CFR 820.72(b). For example, your firm did not complete a nonconformity report in accordance with QOP-83-01, Control of Nonconforming Product, when the (b)(4) used by your firm was found to be out of tolerance prior to calibration. The machine was taken out of service on April 8, 2010. The last calibration of the equipment was completed on November 21, 2008. The (b)(4) was used between November 21, 2008 and April 8, 2010 for in-process testing on (b)(4) medical devices including Tibial Inserts and Femoral Components.
The adequacy of your firm’s response dated May 5, 2011, cannot be determined at this time. The response provides projected dates for issuing a NCR documenting the (b)(4) calibration tolerance issue and the opening of a corrective action.
10. Failure to validate computer software for its intended use according to an established protocol, as required by 820.820.70(i). Your firm uses the (b)(4) for in-process and final product testing for the (b)(4) and the (b)(4). Your firm conducted software validation for the (b)(4) and the results are included in the Software Validation Report, dated February 11, 2010. The (b)(4). The validation compared the measurement of the (b)(4) with the optical comparator and the air gage for the femoral knee on the (b)(4). However, your firm uses the (b)(4) for conducting a surface a (b)(4) during the (b)(4). The (b)(4) is used for measuring the top profile on the (b)(4) during manufacturing. The software validation of the (b)(4) did not address (b)(4).
The adequacy of your firm’s response dated May 5, 2011, cannot be determined at this time. As per your response your firm has completed software validation on theirs(b)(4) but it did not directly validate the types of features that you are using in measuring with the (b)(4) Your response references a projected completion date to work with the manufacturer of the software to develop a validation plan for the (b)(4)
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations 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 money penalties. Also, 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, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
We are requesting that you submit to this office on the schedule below, certification by an outside expert consultant that he/she has conducted an audit of your establishment’s manufacturing and quality assurance systems relative to the requirements of the device QS regulation (21 CFR, Part 820). You should also submit a copy of the consultant’s report, and certification by your establishment’s Chief Executive Officer (if other than yourself) that he or she has reviewed the consultant’s report and that your establishment has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections and subsequent certifications of updated audits and corrections (if required) should be submitted to this office by the following dates:
• Initial certifications by consultant and establishment (b)(4)
• Subsequent certifications (b)(4)
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 documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
Your response should be sent to: Catherine V. Quinlan, Compliance Officer, Food and Drug Administration at 300 River Place, Suite 5900, Detroit, Michigan 48207. If you have any questions about the content of this letter please contact Mrs. Quinlan at (313)393-8153.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations 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 Observation, Form FDA 483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious 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.
Sincerely,
/s/
Kathleen Sinninger
Acting District Director
Detroit District
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