| Public Health Service Food and Drug Administration |
| Dallas District 4040 North Central Expressway Dallas, Texas 75204-3128 |
Department of Health and Human ServicesJuly 20, 2010
Ref: 2010-DAL-WL-12
WARNING LETTER
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Mr. David B. Freehill, President and Co-Owner
Eminent Spine, LLC
7200 North Interstate 35, Building 1
Georgetown, Texas 78626
Dear Mr. Freehill:
During an inspection of your firm located at the above-referenced address on March 1 through March 9, 2010, investigators from the United States Food and Drug Administration (FDA or Agency) determined that your firm manufactures and distributes Intervertebral Body Fusion Systems (IBFS) consisting of the four configurations of the PEEK-OPTIMA® implant spacers (Copperhead®, Python TM, Sidewinder™, and Cottonmouth®) and the surgical instruments (rasps, trials, shavers, hammers, packing blocks, and inserters) that are indicated for intevertebral body fusion of the lumbar spine. Under Section 201 (h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321 (h), these products are medical 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 any 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.
At the conclusion of the Inspection, the investigators issued to you the Form FDA-483 (List of Inspectional Observations) which identifies a number of significant violations including, but not limited to, those described below.
We received your response, dated March 29, 2010, to our investigators' inspectional observations. We acknowledge your commitment to implement various corrective actions to resolve the noted observations. However, we consider your response incomplete as you have not provided documentation or evidence that demonstrates your completion and verification of the corrective action activities you promised. Please provide us an update on the progress of your firm's corrective actions. The Agency will conduct follow-up inspections to assure that your firm's corrections are adequate.
Quality System Violations
1. Failure to establish and maintain procedures to identify, document, evaluate, segregate, and dispose of products that do not conform to specifications, as required by 21 C.F.R. § 820.90(a). FDA 483 Item 3. Specifically:
Five of the (b)(4) device history records (DHRs) the investigators reviewed showed that the Copperhead spine implants did not meet their approved dimensional specifications during the in-process inspections conducted by your contract manufacturer. Your firm accepted these potentially nonconforming implants without evaluating, investigating, and documenting a justification for accepting them. For example, the DHR for Work order #ES1350 showed that six of the (b)(4) implants exceeded the tolerance for Dimension A. The DHR for Work Order #ES-1209 showed that eight implants exceeded the tolerance for the depth of the teeth.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. You stated that each material will be evaluated on its conformance and any out-of-specification products that were accepted will be thoroughly assessed and that a justification for acceptance of each nonconforming material will be prepared and attached to the acceptance of nonconformance documentation. You further stated that a full review of all DHRs will take place and a formal DHR review will be completed by May 4, 2010.
2. Failure to establish and maintain adequate procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria prior to releasing the devices for distribution and for documenting the acceptance results, as required by 21 C.F.R. §§ 820.80(d) and (e). FDA 483 Item 2. Specifically:
Your firm has not established procedures for the inspection and cleaning of the surgical instruments and unused implants of the IBFS returned to your firm from user facilities after use in surgery. You stated that your firm had previously cleaned and inspected these returned devices for re-distribution (the devices are labeled unsterile and are to be sterilized at the user facility before use). For example, the investigators observed a reddish brown stain on inner threads of an inserter of the returned Sidewinder IBFS (Lot #SW112). The inserter is used to hold the implant during surgery. In another instance, the investigators observed a powdery white substance on the heads of a rasp and a trial of the returned Copperhead IBFS (lot #CH112). When asked by the investigators, your firm re-cleaned the devices and easily removed the reddish-brown substance.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. You stated that your firm will develop a new receiving inspection procedure and conduct face-to-face training session with all sales representatives and in-house staff and emphasize the importance of following the cleaning, inspection, and sterilization instructions provided in the Instructions for Use (IFU) of device' labeling. You will also conduct and document a training session on how to avoid exposure to blood-borne pathogens. These activities were to have been completed by May 7, 2010.
3. Failure to establish and maintain procedures for validating the device design in order to ensure that the devices conform to defined user needs and intended uses. The design validation must include testing of production units under actual or simulated use conditions, and risk analysis, where appropriate, and the design validation results must be documented, as required by 21 C.F.R. § 820.30(g). FDA 483 Item 1. Specifically:
a. Your design validation does not include validation of multiple autoclave sterilization cycles on your IFBS devices to determine the effects of multiple (repeat) sterilization cycles on the functionality and specifications of the unused implants of varying sizes. You explained that as per the IBFS labeling your sales representatives will ensure that the user sterilizes the implants prior to surgery, that the unused implants in the IBFS tray are sterilized after surgery, that your sales representatives will then refill the tray with replacement implants and deliver the tray to the next surgery, and that this cycle continues until the IBFS is removed from service.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. During the inspection, you asked the supplier to provide their validation report to show that the mechanical properties of the PEEK:Optima implant material remain well within specifications following (b)(4) hours of steam sterilization or (b)(4) operating room entries with sterilization pre-surgery and post-surgery. However, you did not explain whether your firm has conducted measurements of the implants' dimensional specifications and 'fit testing after repeat autoclave sterilizations to ensure that dimensional specifications remain unchanged. In your response, you agreed to perform a multiple-cycle sterilization validation, conduct testing of device functions post sterilization cycles, and complete the validation report in the next six to twelve months. Additionally, you stated that your firm would implement a system to track the number of sterilizations per implant and complete this task by June 7, 2010.
b. Your firm has not validated the cleaning procedure recommended in the instructions for use (IFU) of the IBFS devices for the surgical instruments (hammers, shavers, rasps, and inserters) to ensure that the cleaning procedure effectively remove body fluids and tissue debris from the instruments after surgery.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. You stated that your firm will prepare a draft protocol for validation for the cleaning (reprocessing) procedure that the validation study will be conducted b an outside laboratory, and that the validation will include the (b)(4) which is considered to be the worst case because it has the (b)(4) and is the most difficult to clean, and that the final validation report will be made available by June 30, 2010. We suggest you also consider validating the same cleaning procedure for the bone shaver as it has the same potential for retaining tissue debris.
4. Failure to validate and document with a high degree of assurance the results of a process that cannot be fully verified by subsequent inspection and test, and failure to have established procedures for such activities, as required by 21 C.F.R. § 820.75(a). FDA 483 Item 3 and 5. Specifically:
Neither your firm nor your contract manufacturer has validated the machine milling process used to mill your IBFS implants in order to ensure that the implants consistently meet their approved specifications. Further, your firm and the contract manufacturer have not measured all dimensional specifications of the implants in their initial production lots and maintain their inspection results to verify the consistency of the milling process.
For example, as referenced in FDA 483 item 3, five of the (b)(4) device history records (DHRs) showed that your firm accepted the Copperhead implants that did not meet their approved dimensional specifications during the in process inspections conducted by your contract manufacturer.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. You stated that production processes for the implants and inserters that cannot be fully verified will be validated by the critical supplier with oversight by your firm, that your firm's requirement for process validation will be established through implementation of critical supplier contracts, that process changes will require prior notification to your firm, and that your firm will establish a more robust incoming inspection process for the receiving products. You expect to complete these correction activities by December 31, 2010.
5. Failure to establish and maintain procedures to ensure that design requirements relating to a device are appropriate and address the intended use of the device, including the needs of the user and patient, and failure to ensure that the design input requirements shall be documented, reviewed, and approved by designated individual(s), as required by 21 C.F.R. § 820.30(c). FDA 483 Item 4. Specifically:
Your firm has not defined and documented the design input requirements for the surgical instruments (accessories) included in the Copperhead Intervertebral Body Fusion Systems (IBFS) and the Fang Buttress Plate System.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. You stated that the inserter included in the IBFS is (b)(4) and you will conduct a full review and remediation that will address all design control elements (input, output, review, verification, validation, transfer, and design change) associated with the implants and the inserters. You expect to complete this correction activity by July 30,2010.
6. Failure to establish and maintain device master records (DMRs) to include or refer to the location of device specifications, production process specifications, quality assurance procedures, and packaging and labeling specifications, and to ensure that each DMR is prepared and approved in accordance with 21 C.F.R. § 820.40, as required by 21 C.F.R. § 820.181. FDA 483 Item 13. Specifically:
Your firm does not have a device master record for your Intervertebral Body Fusion System (IBFS) and Fang Buttress Plate System.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. You stated that device master records were being established and would be completed by May 7, 2010.
7. Failure to define the type and extent of control to be exercised over the product, services, suppliers, contractors, and consultants, as required by 21 C.F.R. § 820.50(a)(2). FDA 483 Item 12. Specifically:
Your firm does not have documentation (SOPs, contract, or an agreement) that defines what manufacturing and acceptance activities are to be performed by your contract manufacturers of the implants and surgical instruments.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. You stated that your firm will establish critical supplier agreements by April 30, 2010, and will implement quality assurance procedures to assure that the suppliers adhere to these agreements.
8. Failure to conduct and document quality audits to assure that the quality system is in compliance with established quality system requirements and to determine the effectiveness of the quality system, as required by 21 C.F.R. § 820.22. FDA 483 Item 7. Specifically:
Your firm has not conducted and documented a formal quality audit of your firm's quality system since November 2008.
Your response is incomplete as you have not provided documentation that verifies the corrective actions as follows. You stated that you will hire a consulting firm to conduct comprehensive quality system audits (b)(4). Please provide an update on your accomplishment since your April 2010 audit.
Responding to This Warning Letter
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in enforcement action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or 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, pre-market approval applications for Class III devices to which the Quality System regulation (21 CFR Part 820) deviations are reasonably related will not be approved until the violations related to the subject devices have been corrected.
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 and 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 correction will be completed.
Your response should be sent to Thao Ta, Compliance Officer, Dallas District Office, Food and Drug Administration, HFR-SW140, 4040 North Central Expressway, Suite 300, Dallas, Texas 75204. If you have any questions about the content of this letter, please contact Mr. Ta at 214-253-5217.
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 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/
Reynaldo R. Rodriguez
Dallas District Director
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