Cantor & Nissel Ltd.
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Department of Health and Human Services
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Food and Drug Administration
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September 27, 2011
VIA UNITED PARCEL SERVICE
Cantor & Nissel, Ltd.
Dear Mr. Cantor:
During an inspection of your firm located in Brackley, Northamptonshire, United Kingdom, on April 26 through April 28, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Daily Wear Soft Contact Lenses. 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 (CFR), Part 820. We received a response from your firm dated May 16, 2011, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that 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 maintain adequate complaint files and establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).
The procedures shall ensure that:
a. All complaints are processed in a uniform and timely manner;
b. Oral complaints are documented upon receipt; and
c. 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.
For example, your firm has no written complaint handling procedures. Instead, complaints are recorded on the corrective and preventive action (CAPA) form.
Your firm’s response did not address this observation because it was not listed on the FDA 483.
2. Failure to establish and maintain schedules for the adjustment, cleaning, and other maintenance of equipment to ensure that manufacturing specifications are met. Maintenance activities, including the date and individuals performing the maintenance activities, shall be documented, as required by 21 CFR 820.70(g)(1).
For example, your firm’s personnel stated (b)(4)
We reviewed your firm’s response and conclude that it is adequate.
3. Failure to establish and maintain adequate procedures for verifying or validating corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4).
We reviewed your firm’s response and conclude that it is not adequate. Section 6.7 of your firm’s Corrective and Preventive Action procedure (b)(4) states that a follow–up verification will be done to assess and determine the effectiveness or any adverse effect to the final product. However, (b)(4) does not address validation of corrective and preventive actions.
Our inspection also revealed that your firm’s ChromaGen V2.0 Haploscopic System & Color Discrimination Enhancement Soft Lens 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 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 (MDR). Significant violations include, but are not limited to, the following:
Failure to have an adequate written MDR procedure establishing internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements, as required by 21 CFR § 803.17(a)(1).
A review of your firm’s MDR procedure identified the following deficiencies
- Your firm’s procedure does not define “cause or contributed” and “serious injury,” as stated in 21 CFR 803.3. The exclusion of these terms in the procedure may lead the firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
- Your firm’s procedure does not include a process for identifying and evaluating events occurring outside the U.S. as potentially reportable to FDA, as required by 21 CFR 803.50 and 803.53. If an event occurs in a foreign country, it may be reportable under the MDR regulation if the event involves a device that has been cleared or approved in the U.S. and is also lawfully marketed in a foreign country. Devices may be manufactured to slightly modified specifications to meet standards in different countries. If these changes do not substantially alter the performance of the device, then any adverse event that are MDR‑reportable events relating to such modified devices should be reported under the MDR regulation. By not considering events that occur outside of the U.S., potentially reportable MDRs may not be identified and evaluated for MDR decision making and submission to FDA as required by 21 CFR 803.50 and 803.53.
- As initial distributors, (b)(4) only need to keep MDR files as required by 21 CFR 803.18(d). If the two firms act as initial importers for your firm, then they must comply with the requirements in 21 CFR 803.17, 803.18, 803.40, and 803.42. However, your firm, (b)(4) may request an exemption under 21 CFR 803.19 that will allow the submission of one MDR for events in which your firm, (b)(4) have an obligation to submit a report to FDA.
- Under 6.3, of your procedures, Criteria for Reporting Within the US, your firm’s procedure states, (b)(4) This statement may lead to incorrect MDR decisions. As stated in 21 CFR 803.50(b)(3), the manufacturer is responsible for conducting an investigation of an event and evaluating its cause to determine whether the complaint should be reported to FDA.
- Your firm should make an MDR decision based on information obtained during the course of its investigation and evaluation of the cause of the event.
We have the following recommendation:
- The Medical Device Reporting requirement for Baseline Reporting was repealed under a rule that became effective on October 27, 2008. Therefore, the reference to Baseline Reporting in Section 6.6, Information to be reported for incidents occurring within the USA, can be removed from your firm’s procedure.
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. 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 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 action (including any systemic corrective actions) 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 Operations Branch, White Oak Building 66, Rm 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #207433 when replying. If you have any questions about the contents of this letter, please contact: Mr. Ronald L. Swann at (301) 796-5770 or (301) 847-8137.
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.
Steven D. Silverman
Office of Compliance
Center for Devices and