- Herniamesh S.r.l
- 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
NOV 23, 2015
VIA UNITED PARCEL SERVICE
Lorena A. Trabucco
President, U.S. Agent
540 Muttontown Eastwoods Road
Syosset, New York 11791
Dear Ms. Trabucco:
During an inspection of your firm located in Chivasso, Italy,on July 20, 2015, through July 23, 2015, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures polymeric surgical meshes. 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 in conformity 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 your response from Dr. Selanna Martorana, dated July 30, 2015, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address these responses 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 receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example:
a. Your firm’s complaint handling procedure, “Genstione Dell Non Conformita,” Revision G, dated July 8, 2015, does not require that:
i. Oral complaints are documented upon receipt
ii. Complaints are evaluated to determine whether the complaint represents an event which is required to be reported to FDA under part 803, Medical Device Reporting (MDR)
iii. When an investigation is made, that complaint investigation records must include:
1) The name, address, and phone number of the complainant,
2) The dates and results of the investigation, and
3) Any reply to the complainant.
b. Complaints, including complaint numbers #15/033, #15/015, #14/053, and #14/066, for the T-Sling device, were not evaluated for MDR.
We reviewed your firm’s response and conclude that it is not adequate. Your firm states that it is reviewing the identified complaints for MDR reporting. However, there was no retrospective review of other complaint records to ensure that their documentation is complete and that evaluations for MDR reportability were completed appropriately. Additionally, your firm’s response states it has updated its complaint handling procedure to include the missing requirements from 21 CFR 820.198; however, the procedure was not provided.
2. Failure to adequately ensure, that 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, your firm’s Tyvek (b)(4) process, using (b)(4), has not been adequately validated. Your firm manufactures multiple surgical mesh sizes that use different Tyvek package sizes. However, your firm only validated the (b)(4) for one Tyvek package size. Additionally, your firm did not document which medical device and package size was used in this validation.
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response states it will validate the (b)(4) process and establish a monitoring procedure for validated processes. However, your firm’s response does not include a risk analysis to determine the potential effects of the unvalidated processes on the devices. Additionally, your firm’s response does not include a retrospective review of complaints to determine if devices may have failed as a result of an inadequately controlled process.
3. Failure to establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met, as required by 21 CFR 820.75(b). For example, your firm has identified the (b)(4) sterilization, (b)(4) Process as requiring validation. However, your firm does not have a procedure for monitoring validated processes, and your firm does not identify the data to be monitored; control limits; or how the data generated from the monitoring of the validated processes shall be reviewed and analyzed.
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response states it will validate the (b)(4) process and establish a monitoring procedure for validated processes. However, your firm’s response does not include a risk analysis to determine the potential effects from inadequate (b)(4) on safety and effectiveness of your firm’s devices. Additionally, your firm’s response does not include a retrospective review of complaints to determine if any were the result of an inadequately controlled process.
4. Failure to establish and maintain procedures for acceptance of incoming product, as required by 21 CFR 820.80(b). For example:
a. Your firm’s Work Instruction for (b)(4) acceptance, “IDL003,” Rev. H, dated (b)(4), 2008, does not have a statistical rationale for sampling as required by 21 CFR 250(b). The procedure requires (b)(4) visual inspection, (b)(4) for relative density tests. The average (b)(4) size for (b)(4) is approximately (b)(4) square meters.
b. Your firm’s Work Instruction for Tyvek acceptance, “IDL006,” Rev. D, dated (b)(4), 2007, does not have a statistical rationale for sampling as required by 21 CFR 250(b). The procedure requires sampling for (b)(4), and (b)(4) tests of (b)(4) units/lot, where lots are an average of (b)(4) units.
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response states it is planning to create a procedure to justify sampling criteria for acceptance activities. However, your firm’s response does not include a risk analysis/evaluation of the potential impact of using nonconforming materials or components in the finished device. Additionally, your firm’s response does not include a retrospective review of complaints to determine if inadequate receiving acceptance activities may have resulted in complaints.
5. Failure to validate computer software, when used as part of production or the quality system, for its intended use according to an established protocol, as required by 21 CFR 820.70(i). For example:
a. Your firm did not validate “(b)(4)” software for its intended use in the quality system. This software is used for documenting identification listing; manufacturing management of instruments and equipment; calibration planning and records; supplier listing and evaluation; and management of nonconformities and (b)(4).
b. Your firm did not validate “(b)(4)” software for its intended use in the quality system. This software is responsible for purchasing, logistics, and production, including bill of materials and lot records.
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response states that it will conduct a retrospective validation for the software by the next management review. However, your firm’s response did not include a retrospective review of production or quality system software to determine that other software is appropriately validated.
6. Failure to establish calibration procedures that include specific directions and limits for accuracy and precision, as required by 21 CFR 820.72(b). For example, the indicated range for use of the (b)(4) is (b)(4). However, your firm’s (b)(4) was calibrated at a range of (b)(4).
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response states it is updating its equipment requirements to specify a (b)(4) range, as the initial limits were incorrect. However, your firm’s response does not include a retrospective review of your firm’s equipment calibration records to show that equipment is appropriately calibrated.
Our inspection also revealed that the Polymeric Surgical Mesh is 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 regarding the devices 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 deviations include, but are not limited to:
7. Failure to report to us no later than 30 calendar days after the day that it received or otherwise became aware of information, from any source, that reasonably suggests that a device that the firm markets may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1).
a. Complaint #14/053 describes an event where the patient incurred injuries, urinary incontinence, urinary retention, and recurring urinary tract infections that were treated with prescription medications. The information reasonably suggests that the device may have caused or contributed to injuries that necessitated medical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.
b. Complaint # 14/066 describes an event where the patient experienced profuse vaginal bleeding and developed rectal prolapse. Hemostasis was achieved for the profuse vaginal bleeding and the rectal prolapse was treated. The information reasonably suggests that the device may have caused or contributed to the injuries that necessitated medical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.
8. Failure to adequately develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17(a). After reviewing your firm’s MDR procedure, titled “Medical Device Reporting”, PRO026, Rev. B, the following issues were noted:
a. (b)(4), Rev. B 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, the procedure omits the definition of the term “reasonably suggests” found in 21 CFR 803.20(c)(1). The exclusion of the definition for this term from the procedure may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
b. (b)(4), Rev. B does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, your firm did not address the circumstances under which your firm must submit supplemental or follow-up reports and the requirements for such reports.
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response states that it will re-analyze Medwatch reports received between 2012 and 2014, as well as review the MDR procedure to ensure compliance with the 21 CFR Part 803 regulatory requirements. However, your firm has not provided documentation for review.
Given the serious nature of the violations of the Act, polymeric surgical meshesmanufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States, known as “detention without physical examination,” until these violations are corrected. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violation(s) described in this letter. 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.
U.S. federal agencies may be advised of the issuance of 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.
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) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen 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.
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, Rm 3523, 10903 New Hampshire Ave., Silver Spring, MD 20993.
Refer to CMS case #480085 when replying. If you have any questions about the contents of this letter, please contact: LT David Dar, Acting Chief, Foreign Enforcement Branch, at firstname.lastname@example.org (email) or +1(240)402-4020 (telephone).
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 Inspectional 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.
CAPT Sean M. Boyd, MPH, USPHS
Office of Compliance
Center for Devices and Radiological Health
Cc: Selanna Martorana
QA/R&D & Regulatory Manager
Via Fratelli Meliga 1/C
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