- Corin Ltd
- Issuing Office:
- Center for Devices and Radiological Health
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||10903 New Hampshire Avenue|
White Oak Building 66
Silver Spring, MD 20993
SEP 14, 2015
VIA UNITED PARCEL SERVICE
Mr. Stefano Alfonsi
Chief Executive Officer
Corin Medical Ltd.
Dear Mr. Alfonsi:
During an inspection of your firm located in Cirencester, United Kingdom, on March 2, 2015, through March 5, 2015, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures knee prosthesis systems. 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 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 inconformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
We received a response from Mr. Barry Taylor, Quality Assurance Manager, dated March 26, 2015, concerning our investigator's observations noted on the Form FDA 483 (FDA 483), List of lnspectional Observations, which was issued to your firm. 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 for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, three CAPA records originating from production did not include verification of the effectiveness of corrective actions, or verification that the corrective action did not adversely affect the finished device.
The adequacy of your firm's response cannot bedetermined at this time. Your firm updated CAPA related procedures/forms and indicated that trainings will be conducted. Your firm indicated that it will perform a retrospective review of previous CAPA investigations to identify any other instances of incomplete or inadequate verification of corrective actions for effectiveness, and confirm there were no adverse effects on the finished device. However, adequacy cannot be determined without review of the documentation of these activities.
2. Failure to establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820.80(d). For example, your firm performs a 100% visual inspection of the polished surface for surface roughness of the Unity Knee CR Femur Part No. 112.001.14. However, there is no assurance that "Guidelines for Visual Acceptance Standards," STM 04, is adequate for identifying surface defects on Unity Knee CR Femur products without using surface testing equipment.
The adequacy of your firm's response cannot be determined at this time. Your firm indicated that it created and executed a protocol for validation of surface roughness of implants according to ISO 72072-2011. However, adequacy cannot be determined without review of documentation of these activities.
3. Failure to ensure that where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a). For example, the (b)(4) dimensions meet specified requirements.
The adequacy of your firm's response cannot be determined at this time. Your firm indicated that it created a protocol for process validation of dimensional features not currently subject to 100% verification, including the (b)(4) Unity inserts. However, adequacy cannot be determined without review of documentation of these activities.
4. Failure to adequately establish and maintain procedures that define the responsibility for review and the authority for disposition of nonconforming product, as required by 21 CFR 820.90(b). For example, during dimensional inspection associated with Engineering Change Request No. 13426, three measured dimensions were found to be out of tolerance. The product was accepted and released based on a technical review that "(b)(4)." Your firm's statement does not constitute adequate documentation of justification for the use of nonconforming product because the documented justification does not include sufficient evaluation to ensure that the out of tolerance dimensions will not affect device functionality.
We reviewed your firm's response and conclude that it is not adequate. Your firm performed a FMEA risk review to assess the safety and effectiveness of the machine (b)(4). Your firm indicated that it will update procedures/forms to define the structure for applying risk review and conduct trainings. However, your firm did not evaluate previous Engineering Change Requests, and other nonconforming product forms, to ensure documentation of justification for use of nonconforming product, where applicable. Also, your firm did not provide all evidence of corrective action for review.
5. Failure to document acceptance activities, as required by 21 CFR 820.80(e). For example, incoming records for the (b)(4), for femurs and tibias for Unity Knee, do not include documentation (b)(4), required per Section 4.4.4 of "Purchase Specification," CPS 053.
The adequacy of your firm's response cannot be determined at this time. Your firm performed a retrospective review and contacted the supplier to confirm that (b)(4) was successfully completed on all received batches. Your firm indicated that it will compare Purchasing Specification test requirements, Certificate of Conformity requirements, and Goods Inwards Inspection verification requirements, to identify any variances. However, adequacy cannot be assessed without documentation of these activities.
6. Failure to establish and maintain procedures for verifying the device design, as required by 21 CFR 820.30(f). For example, the following design verifications for the Unity Knee were made without acceptance criteria:
a. Approved Report No. 541 documented testing (b)(4);
b. Approved Report No. 543 documented (b)(4).
We reviewed your firm's response and conclude that it is not adequate. Your firm completed supplemental reports for Approved Reports Nos. 541 and 543. Your firm updated design controls procedures and indicated that trainings will be conducted. However, a retrospective review of design verification test reports to ensure that all reports contain qualitative and quantitative acceptance criteria was not provided.
Our inspection also revealed that the knee prosthesis systems 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 (MDR). These violations include but are not limited to the following:
7. Failure to submit a report to FDA no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device it markets has malfunctioned and this device or a similar device that it markets would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur, as required by 21 CFR 803.50(a)(2). For example, Complaint Nos. 826 and 986 describe a malfunction of your firm's long-term implant. Your firm did not rule out that such malfunctions would not be likely to cause or contribute to a death or serious injury, if they were to recur. Therefore, an MDR should have been submitted for each of the referenced complaints.
We reviewed your firm's response and conclude that it is not adequate. Your firm did not submit MDRs for the above referenced complaints.
The eMDR Final Rule requiring manufacturers and importers to submit electronic Medical Device Reports (eMDRs) to FDA was published on February 13, 2014. The requirements of this final rule will take effect on August 14, 2015. If your firm is not currently submitting reports electronically, we encourage you to visit the following web link for additional information about the electronic reporting requirements: http://www.fda.gov/Forlndustrv/FDAeSubmitter/ucm107903.htm.
If your firm wishes to discuss MDR reportability criteria or to schedule further communications, it may contact the Reportability Review Team by email at ReportabilityReviewTeam@fda.hhs.gov.
Please notify this office in writing, within fifteen business days from the date you receive this letter, of the specific steps your firm has taken to correct the noted violations, including an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems)your firm has taken. If your firm's planned corrections and/or corrective actions will occur over time, please include a timetable for implementationof those activities. If corrections and/or corrective actions cannot be completed within thirty business days, state the reason for the delay and the time within which these activities will be completed. Please provide a translation of documentation not in English to facilitate our review. We will notify you regarding the adequacy of your firm's response(s) and the need to re-inspect your firm's facility to verify that the appropriate corrections and/or corrective actions have been made.
Your firm's response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Inspections Support Branch, White Oak Building 66, Room 2622, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #461343 when replying. If you have any questions about the contents of this letter, please contact: Daniel Walter, Chief, Foreign Enforcement Branch, at +1 (240) 402-4020 (phone) or +1 (301) 847-8139 (fax).
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm's facility. It is your firm's responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the lnspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality management systems. Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.
Jan B. Welch, MHS, MT (ASCP) SBB Acting Director
Office of Compliance
Center for Devices and
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