Inspections, Compliance, Enforcement, and Criminal Investigations
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
555 Winderley Place, Suite 200
Maitland, Florida 32751
w/ DELIVERY CONFIRMATION
May 31, 2013
W. King Floyd
1300 Minnesota Avenue, Suite 200
Winter Park, Florida, 32789-4800
Dear Mr. Floyd:
During an inspection of your firm located in Winter Park, Florida, on January 29, 2013, through February 1, 2013, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is the specification developer of the SpineNet ACC (Anterior Cervical Cage) System; an importer/repacker/relabeler of Apollon and Vane Pedicle Screw Systems; and a relabeler/distributor of the SpineNet Bone Marrow Aspiration Needle Kit. 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 is intended to affect the structure or function of the body.
The current 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, its 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 written response from you on February 22, 2013, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations, which was issued to you. We address this response below, in relation to each of the noted violations. The violations include, but are not limited to, the following:
Quality System Regulation
1. Failure to adequately ensure, when the results of a process cannot be fully verified by subsequent inspection and test, that the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a).
For example: You indicated to our investigator during the inspection that the recommended sterilization cycles in your “Instructions for Use” (IFU) for the SpineNet ACC device were not validated. On IFU-ACC-01, your firm recommends a fractionated (b)(4) cycle and a (b)(4) cycle for sterilization of the SpineNet ACC device.
We reviewed your firm’s response and conclude that it is not adequate, in relation to the noted violation. Your firm provided a quote and purchase order for validation of recommended sterilization cycles. Your firm failed to provide a copy of your validation procedures; failed to indicate why these sterilization cycles were not validated; and failed to provide evidence that your firm has implemented a corrective action to ensure that this does not recur. Also, your firm did not indicate whether it has reviewed other processes requiring validation to ensure that they were validated as part of a systemic corrective action.
2. Failure to establish and maintain adequate procedures to ensure all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50.
For example, during the inspection, you indicated that your firm failed to:
- Complete purchasing control requirements per your procedure for Solco Biomedical, the supplier of Vane and Apollon implants that you repack, relabel, and distribute.
- Obtain a completed Supplier Self Evaluation from (b)(4), your supplier of PEEK (Zeniva ZA-500 & 600), a raw material used to manufacture your SpineNet ACC implants.
The adequacy of your firm’s response cannot be determined at this time. Your firm provided a copy of the revised SOP 8 Purchasing Controls procedure. Your firm provided a revised Approved Supplier List in which, you added your implant supplier, Solco Biomedical. The status of the firm was listed as “Approved”. You did not provide documentation of how the firm was added with an “Approved” status. Additionally, your response indicated your firm will ask all approved suppliers to complete revised Supplier Self Survey forms with 3-4 weeks; however, you did not propose interim corrective actions or consideration of systemic corrective actions.
3. Failure to maintain adequate procedures for acceptance of incoming product. Incoming product shall be inspected, tested, or otherwise verified as conforming to specified requirements. Acceptance or rejection shall be documented, as required by 21 CFR 820.80(b). You verbally confirmed during the inspection that your firm failed to establish acceptance activities to address incoming inspection of components, instrumentation, finished implants, and returned goods.
- You stated to our investigator that your SpineNet ACC implant has teeth which are designed to keep the implant from migrating out of position in the body and that your firm does not include the inspection of this required attribute on incoming finished implants received from your contract manufacturer.
- You stated to our investigator that your firm uses Certificates of Conformance from the suppliers to verify conformance of components and that you do not have a procedure stating what elements on the certificate should be verified.
- You stated to our investigator that your firm does not have written documentation or a written incoming procedure for the inspection of finished implants supplied by Solco Biomedical.
- You stated to our investigator that your firm does not have a written incoming inspection procedure for inspection of returned goods received by your firm. Additionally, you stated the status of returned goods is not checked or documented until the returned item is inspected for damage, before being shipped to another customer.
The adequacy of your firm’s response cannot be determined at this time. Your firm did not include documentation or evidence of the corrections, corrective actions, or consideration of systemic corrective actions in the response to FDA, including completion of acceptance activities.
4. Failure to adequately establish procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). You verbally confirmed to our investigator, during the inspection that your firm does not have a complaint procedure to ensure timely processing of complaints, investigation of complaint, and MDR review of complaints.
- Complaint #3 dated June 15, 2012, references a doctor was trying to get an Apollon rod (part of the Apollon Pedicle Screw System) to go thru an offset construct and torqued the rod, breaking it. You did not document whether the rod tip broke inside the patient or if tip was required to be retrieved from inside the patient to facilitate MDR review. You stated this complaint investigation was ongoing.
- Complaint #4 dated January 18, 2013, references a Vane Crosslink that opened on one side of the hook during initial surgery. As the initial importer of this device, you did not document an MDR review of this complaint. You stated this complaint investigation was closed.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a copy of SOP 15, Complaint Handling; a Complaint Log containing four complaints; and additional information received for Compliant #3. This response does not include a retrospective review of complaints to determine if complaint investigations were completed with enough information to facilitate MDR review. Additionally, your firm has listed Complaint #3 as closed without providing documentation of an MDR review and the completion of the forms required by your revised procedures.
5. Failure to establish 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: Your firm’s Internal Audits Procedure, SOP #11 Rev. A, dated August 2, 2010, requires every activity and area subject to an internal quality audit at least once a year, however, you stated to our investigator during the inspection that your firm has not completed any internal quality audits to date. Additionally, your firm's Internal Audits Procedure requires an internal quality audit plan to identify specific audit criteria that will be covered during internal quality audits including dates and times of audits and auditors that was not created.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a revised copy of its Internal Audit Procedure which includes an Internal Audit Summary. Your response also lists March 20, 2013, as the date of completion of your annual internal audit; however your response does not include identification of the audit plan to include dates and time of quality audit and audit criteria as required by your procedure. Additionally, your firm did not provide evidence that a corrective action (including review of all auditing requirements to ensure that they will be completed as required) will be implemented.
6. Failure to adequately establish and maintain procedures for implementing corrective and preventive action (CAPA), as required by 21 CFR 820.100(a).
For example: Your firm's Corrective and Preventive Action (CAPA) Procedure, SOP #13 Rev. A, dated August 2, 2010, lacks requirement to verify and/or validate effectiveness of corrective and preventive actions and that the CAPA's will not adversely affect the finished device.
We reviewed your firm’s response and conclude that it is not adequate. Your response discusses the implementation of numerous corrections to address the violations observed during the inspection, yet do not provide any documentation that your current CAPA system is robust enough to handle these activities. Additionally, this response does not include a retrospective review of CAPA implemented to determine the effectiveness of the corrective and preventative action and to ensure the actions did not adversely affect the finish device.
7. Failure to establish and maintain adequate procedures to ensure that mix-ups, damage, deterioration, contamination, or other adverse effects to product do not occur during handling, as required by 21 CFR 820.140.
- Your procedure fails to address the risk of contamination/ foreign matter and increase of bioburden caused by routine handling of unpackaged implants by personnel.
- During the inspection, the investigator observed the SpineNet ACC implants stored outside of an immediate package on shelves awaiting orders from customers. You and your quality consultant verbally confirmed personnel are not required to wash hands or wear gloves when handling unpackaged implants in this area.
The adequacy of your firm’s response cannot be determined at this time. Your firm provided a copy of the revised SOP 10 Handling, Storage, Packaging, Preservation, and Delivery procedure, which included the addition of wearing gloves when handling implants outside of packaging. Your firm did not provide documentation of implementation of this correction, such as training of employees on the new practice.
Medical Device Reporting
Our inspection also revealed that your devicesare misbranded under section 502(t)(2) of the Act 21 USC 352 (t)(2), in that your firm failed or refused to furnish material or information respecting the devices that is required by or under section 519 of the Act, 21 USC 360i, and 21 CFR Part 803 – Medical Device Reporting (MDR) Regulation. Significant deviations include, but are not limited to:
Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17. For example, after reviewing your firm’s MDR procedure titled, “SpineNet Standard Operating Procedure Medical Device Reporting (MDR),” SOP#16, Rev A, the following issues were noted:
1. SOP#16, Rev A does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example, there are no definitions of what your firm will consider to be a reportable event under 21 CFR Part 803. To facilitate the correct interpretation of reportable events and to assure the quality of MDR submissions, the procedure should include definitions based on 21 CFR 803.3 for the terms “become aware,” “caused or contributed,” “malfunction,” “MDR reportable event,” and “serious injury,” and definitions for the terms “reasonably known” and “reasonably suggests,” found respectively in 21 CFR 803.50(b) and 803.20(c)(1).
2. SOP#16, Rev A does not establish internal systems that provide for a standardized review process or procedure for determining when an event meets the criteria for reporting under this part. Specifically, there are no instructions for conducting a complete investigation of each event and evaluating the cause of the event.
3. SOP#16, Rev A does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
a. Instructions for how to obtain and complete the FDA 3500A form.
b. The procedure does not include the address for where to submit MDR reports: FDA, CDRH, Medical Device Reporting, P.O. Box 3002, Rockville, MD 20847-3002.
c. The circumstances under which your firm must submit initial, supplemental or follow-up reports and the requirements for such reports.
4. SOP#16, Rev A does not describe how your firm will address documentation and record-keeping requirements, including:
- Documentation of adverse event related information maintained as MDR event files.
- Information that was evaluated to determine if an event was reportable.
- Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable.
- Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
We reviewed your firm’s response datedMarch 29, 2013, and conclude that it is not adequate. Your firm included a revised MDR procedure titled, “SpineNet Standard Operating Procedure Medical Device Reporting (MDR),” SOP#16, Rev B. After reviewing your firm’s revised MDR procedure, the following issue was noted:
1. SOP#16, Rev B does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following was not addressed:
- There are no instructions for how to obtain and complete the FDA 3500A form.
We have the following recommendations:
Please note thatMDR reports cannot be submitted via facsimile. Please revise your firm’s MDR procedure page 3 of 9 to remove the statement “MDR reportable events can be sent via facsimile.”
In addition, your firm’s procedure includes references to baseline reporting and annual certification, which are no longer required. We recommend that all references to Baseline Reports and Annual Certification be removed from your firm’s MDR procedure (see: 73 Federal Register Notice 53686, dated September 17, 2008; and Fourth Notice, Federal Register, dated March 20, 1997: Medical Device Reporting, Annual Certification, Final Rule, respectively).
If your firm,wishes to submit MDR reports via electronic submission it can follow the directions stated at the following URL: http://www.fda.gov/ForIndustry/FDAeSubmitter/ucm107903.htm
If your firm wishes to discuss MDR reportability criteria or to schedule further communications, it may contact the Reportability Review Team of the MDR Policy Branch by email at ReportabilityReviewTeam@fda.hhs.gov.
Our inspection also revealed that the SpineNet Bone Marrow Aspiration Needle Kit, which contains the (b)(4) Bone Marrow Aspiration Needle, is adulterated under Section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to Section 515(a) of the Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. 360j(g). The SpineNet Bone Marrow Aspiration Needle Kit is also misbranded under Section 502(o) the Act, 21 U.S.C. 352(o), in that a notice or other information respecting the modification to the device was not provided to the FDA as required by section 510(k), 21 U.S.C. 360(k), and 21 CFR 807.81(a)(3)(i).
For a device requiring premarket approval, the notification required by Section 510(k) is deemed satisfied when a PMA is pending before the agency, as described in 21 CFR 807.81(b). The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.
During the inspection, FDA collected labeling, including promotional materials, for the SpineNet Bone Marrow Aspiration Needle Kit distributed by your firm. Our review of the materials has determined that your firm is promoting and marketing the SpineNet Bone Marrow Aspiration Needle Kit in the United States for uses with new performance claims and specifications and for a use that does not have FDA clearance or approval. Your firm’s brochure, IFU, and website (www.spinenetllc.com) promote the SpineNet Bone Marrow Aspiration Needle Kit using the following statements:
- “The SpineNet Percutaneous Bone Marrow Harvest Needle kit provides a new and improved way to extract a generous amount of biologic material to fill the spaces in the SpineNet ACC cage. This technique significantly decreases morbidity traditionally associated with obtaining iliac crest graft. SpineNet design surgeons have performed 400 ACDF procedures using this type of cage design and harvest technique with complications less than .005%”
- “Designed to deliver a precise amount of biologic material for the SpineNet ACC”
- “…is intended for use in aspirating bone marrow”
- “…guide the Needle assembly to the bone surface of the iliac crest”
We acknowledge that your firm has chosen to voluntarily recall the product until you have validated that you have the proper clearance for the needle. We also note that all references to the SpineNet Percutaneous Bone Marrow Harvest Needle kit have been removed from your website at http://spinenetllc.com/products/. However, you have failed to provide evidence of the effectiveness of your voluntary recall and that your firm has ceased dissemination of promotional materials for the SpineNet Bone Marrow Aspiration Needle Kit and removed all devices that are labeled with the statements above from your customer base.
Additionally, we acknowledge that your firm has chosen to voluntarily recall the SpineNet ACC devices, as a result of the inclusion of the incorrect instructions for use (IFU) with the device. We received a copy of the corrected instructions for use (IFU) and note that the initial recall communication references replacing the IFU packaged with the devices with the corrected version. However, to date, the FDA has not received a notification of a recall as required by 21 CFR 806, and that the recall must be reported to the FDA as part of the response to this warning letter.
Our inspection also revealed that the Vane and Apollon Pedicle Screw System devices are misbranded under Section 502(o), 21 U.S.C. 352(o), in that the devices were not included in a list required by section 510(k), 21 U.S.C. 360 (j). Significant deviations include, but are not limited to:
Failure to submit listing information for the Vane and Apollon Pedicle Screw System devices, where your firm is acting as a repackager and relabeler, as required by 21 CFR 807.20(a).
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 violations 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 device have been corrected.
Please notify this office in writing within fifteen (15) business days from the date you receive this letter of the specific steps you have taken to correct the noted violations, as well as an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions you have taken. If your planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of these activities. If corrections and/or corrective actions cannot be completed within 15 business days, state the reason for the delay and the time within which these activities will be completed. Your response should be comprehensive and address all violations included in this letter.
Your response should be sent to: Erica M. Katherine, Compliance Officer, Food and Drug Administration, 555 Winderley Place, Suite 200, Maitland, Florida, 32751. If you have any questions about the content of this letter please contact: Erica M. Katherine at (407) 475-4731.
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 Form FDA 483, Inspectional Observations (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management 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.
Emma R. Singleton
Director, Florida District