SpineFrontier, Inc. 8/8/12
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||New England District|
One Montvale Avenue
Stoneham, Massachusetts 02180
(781) 587-7500 FAX: (781) 587-7556
CMS # 334199
VIA UPS Next Day Air
August 8, 2012
500 Cummings Center
Beverly, MA 01915-6126
Dear Mr. Chin:
During an inspection of your firm, SpineFrontier, Inc., located at 500 Cummings Center, Beverly, MA on May 23 through July 11, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a specification developer and repackager of devices that aid in bone fusion, including the S-LIFT Intervertebral Body Fusion Device. 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 (C.F.R.), Part 820.
We received two responses dated July 15 and July 23, 2012, from Christopher Chang, Chief Product Officer, Director of Operations and Alyce Nelson Director of Quality Assurance and Regulatory Affairs, SpineFrontier, relating to our inspection. We do not consider your responses adequate in addressing the investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to your facility. We address your responses below, in relation to each of the noted violations. The violations include, but are not limited to, the following:
1. Failure to establish and maintain procedures for implementing corrective and preventive actions (CAPA’s), as required by 21 CFR 820.100(a). During the inspection, we observed that CAPA’s were not being opened as required by your own procedure. For example, a CAPA was not opened to address the failure of your firm to maintain complaints received prior to January 2012. During the inspection, firm representatives acknowledged that complaints were not maintained properly prior to January 2012, yet no CAPA was generated to address this failure.
2. Failure to establish and maintain procedures for implementing corrective and preventive actions including requirements for investigating the cause of nonconformities relating to product, processes, and the quality system, as required by 21 CFR 820.100(a)(2). For example, your CAPA procedure indicates that CAPA’s should be evaluated within 30 days. For at least (b)(4) out of (b)(4) CAPA’s reviewed, your firm did not meet this requirement and investigations were not assigned until 50 -130 days after issuance.
3. Failure to verify or validate corrective and preventive actions to assure that such actions are effective and do not adversely affect the finished device, as required by 21 CFR 820.100(a)(4). For example, CAPA 103 was initiated on March 3, 2011 to address the impact knob of the SLIF Inserter, Locking shaft (SI50001) breaking off during surgery. The CAPA was closed on May 10, 2011 after indicating that your firm released a new strike plate design on May 5, 2011. We did not observe any verification data to demonstrate this action was effective. We also observed at least two additional similar complaints received after this date and the subsequent issuance of an Advisory Notice to your users on December 23, 2011.
Your response dated July 23, 2012 is inadequate in addressing the above CAPA violations. Your response discusses the implementation of numerous CAPA’s to address the violations observed during the inspection, yet do not provide any documentation that your current CAPA system is robust to handle these activities. Given the above deficiencies, we request assurance that you have corrected the underlying deficiencies with your CAPA system.
The response also notes that you will perform a retrospective review of all closed CAPA’s since 2011. This response is inadequate. In response to this Warning Letter, you should provide your rationale for not including documents earlier than 2011 for your review. We will also require documentation of these reviews when complete and your plan for preventing these CAPA violations from recurring.
4. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a)(1). For example:
- During the inspection your firm acknowledged that complaints were not being maintained and documented properly prior to January 2012.
- For at least (b)(4) complaints reviewed during the inspection, we observed that the investigation referenced different issues or CAPA’s that were unrelated to the initial complaint.
- Your complaint procedure indicates that, if available, the device should be returned for failure analysis to determine the root cause failure of the device. During the review of at least two complaints, it was determined that your firm did not make any attempts to retrieve the device for evaluation.
Your response to this observation is inadequate. You have indicated that you will perform a retrospective review of all closed complaints since 2011. In response to this Warning Letter, you should provide your rationale for not including documents earlier than 2011 for your review. We will also require documentation of these reviews when complete and your plan for preventing these complaint violations from recurring.
5. Failure to establish and maintain procedures for receiving, reviewing and evaluating complaints to determine whether the complaint represents an event which is required to be reported to FDA under 21 CFR Part 803, Medical Device Reporting, as required by 21 CFR 820.198(a)(3). For example, during a review of (b)(4) complaints received by your firm from September 21, 2011 through March 9, 2012, we observed that your firm did not perform a timely review. The time span to review these complaints for MDR reportability ranged anywhere from 38-208 days. We are also concerned by the amount of information being obtained for these complaints as well as and the level of investigation being performed by your firm. This type of information is required by the regulations so that you have ample time to review the incident to determine whether a MDR report is required.
Your response dated July 23, 2012 is inadequate. We understand that you are revising and retraining your personnel on these activities, however we remain concerned that a long term action has not been identified for this corrective action. You will need to provide us with your plans on how you will prevent this violation from recurring.
The response also notes that you will perform a retrospective review of all closed complaints since 2011. This response is inadequate. In response to this Warning Letter, you should provide your rationale for not including open documents earlier than 2011 for your review. We will also require documentation of these reviews when complete and your plan for preventing these violations from recurring.
6. Failure to conduct design validation to ensure that the device conforms to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions, as required by 21 CFR 820.30(g). For example, your firm did not perform any validation to demonstrate that the cases and or caddies used to hold your medical devices, including the S-LIFT Intervertebral Body Fusion Device, can withstand multiple cleaning and sterilization cycles. During the inspection, we observed that you opened a CAPA to deal with numerous reports of silk screening flaking on the cases and caddies, allowing debris to fall into the cases and settle on the instruments.
We understand you are performing validation activities to demonstrate your products can withstand repetitive sterilization cycles. You should provide documentation to our office when this has been completed.
7. Failure to verify your device design by confirming that the design output meets the design input requirements, as required by 21 CFR 820.30(f). For example, in reference to your S-LIFT Intervertebral Body Fusion Device, both the SLIF Verification plan, SF0024 dated August 27, 2010 and the Verification Protocol, VP-4001 dated September 3, 2010, specify that impact testing be performed with and without the inner and outer sleeve of the Inserter. Verification Report TR 10-025, dated September 3, 2010 does not show that the outer sleeve of the Inserter was used during the testing.
Your response is inadequate. You indicate that testing with the outer sleeve is not necessary and that you plan to write a memo to the file justifying this decision. However, you have not addressed how you will prevent this type of violation from recurring. We understand that you are performing an audit of your design history files (DHF) since 2011. In response to this Warning Letter, you should provide documentation that similar errors have not occurred on any previous DHF reports.
8. Failure to establish and maintain purchasing data that assure that you are aware of any changes in the products made by your suppliers that may affect the quality of the finished device, as required by 21 CFR 820.50(b). For example:
- For at least two suppliers, a signed Supplier Quality Plan was not signed prior to them being added to the Approved Supplier List.
- We also observed that your firm’s SOP required that a signed Form FM-105-3 be completed for all of your suppliers. This form indicated that the supplier would notify Spine Frontier of any changes made to their products. During the inspection, firm representatives indicated this firm was no longer being used, yet it was still referenced in your current SOP.
Your response to this violation appears adequate.
Our 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 or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 CFR Part 806 – Reports of Corrections and Removals regulation. Required information regarding the below device correction and removal actions were not sent to FDA within 10 days of initiating a correction or removal as required by 21 CFR 806.10(b). For example:
- On December 23, 2011, you conducted a removal of the SI50001 Lock Shaft, Inserters from the market due to two possible breakages that could occur with this device. This information was not reported to FDA within 10 days.
- On May 14, 2012, your firm requested the retrieval of three lots of the Inspan Compressor Part 11-60004, due to the device breaking along the weld joint. This information was not reported to FDA within 10 days.
During the inspection we observed statements on several of your CAPA’s that suggest you routinely retrieve devices from the field when problems arise. We suggest that you review all of these documents to assure that you are meeting the reporting requirements. This should include any actions you are contemplating to correct the delamination of the silk screening on cases and caddies which hold implants and instruments of your spinal implant systems. Your response discusses that the ink used in the silk screening of these cases, is food grade ink and is safe for human consumption. You also note that the debris from this delamination which may fall onto the implants, does not pose a hazard. You should be assured that all of your devices are free from any extraneous contaminants.
We have reviewed your response and find it inadequate. We understand that you will be addressing your procedures for Recalls and Correction & Removals, yet you have not provided any information to our office regarding the above events. You will need to contact Ms. Susan Liner, NWE-DO Recall Coordinator to provide the appropriate information as required by 21 CFR 806.10(c)(1) for all corrections and or removals that have been conducted by your firm.
Our inspection also revealed that your firm’s devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant violations include, but are not limited to, the following:
Failure to submit a report to the FDA no later than 30 calendar days after the day your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that it markets may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1). For example:
- On August 17, 2011, your firm became aware of a patient death associated with the T8 -KRD1 Pedfuse. This event was not reported to FDA.
- On March 29, 2012, your firm became aware of a device malfunction associated with the Indus Invue Tipped Driver. This event was not reported to FDA until May 21, 2012, 23 days late.
- On April 11, 2012, your firm became aware of a device malfunction associated with the Indus Invue Tipped Driver. This event was not reported to FDA until May 21, 2012, 9 days late.
Your response is inadequate. You did not discuss the filing of the first event as an MDR. We remain concerned that your personnel are trained sufficiently to identify MDR reportable events. We understand that you have hired a third party to assist with the review of MDR’s. In response to this Warning Letter, you will need to provide documentation that adequate MDR procedures are in place and are being adhered to properly by your employees.
You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly correct these violation(s) 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.
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 violation(s), or similar violation(s), 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.
Please direct your response or any questions you may have to Karen Archdeacon, Compliance Officer, Food and Drug Administration, One Montvale Avenue, 4th Floor, Stoneham, Massachusetts 02180. Her telephone number is (781) 587-7491.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) 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 problems in your firm’s manufacturing and quality assurance systems. You should investigate and determine the causes of the violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance.
Mutahar S. Shamsi
New England District
Cc: Aditya S. Humad
Chief Financial Officer, VP of Business Development
500 Cummings Center
Beverly, MA 01915-6126