Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
JUN 29 2012
VIA UNITED PARCEL SERVICE
Maria Nora Gorni
RI. MOS. S.R.L.
Viale Gramsci, N. 29
Mirandola, Italy 41037
Dear Ms. Gorni:
During an inspection of your firm located in Mirandola, Italy, on March 26, 2012, through March 29, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures obstetric anesthesia sets; endometrial suction curettes and accessories; vaginal speculums; forceps; cervical, endo-cervical, and endometrial sampling devices; cannulas for endometrial aspiration; devices for vacuum-assisted fetal delivery; uterine manipulators and injectors; devices for sperm collection, artificial insemination, ovum pick-up in gamete intra fallopian transfer, in vitro fertilization, and embryo transfer procedures; and disposable needles for bone and soft tissues. 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. These violations include, but are not limited to, the following:
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). Specifically, the validation study was incomplete for the (b)(4) which has been used in the packaging process since May 10, 2001. For example, the package integrity evaluations for the post-sterilization devices were not adequately performed. Your firm only performed visual checks of the seals after sterilization to determine the seal joint strength.
2. 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 did not have process validation procedures.
3. Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications. Where deviations from device specifications could occur as a result of the manufacturing process, the manufacturer shall establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications. Where process controls are needed, they shall include documented instructions, standard operating procedures, and methods that define and control the manner of production, as required by 21 CFR 820.70(a)(1). For example, your firm did not have an established procedure for the sealing operation specific to the sealer that was purchased in October 2011.
4. Failure to establish and maintain procedures to adequately control environmental conditions that could reasonably be expected to have an adverse effect on product quality as required by 21 CFR 820.70(c). (b)(4) The components are not adequately protected from dirt, dust and other contaminants, or from inclement weather conditions.
5. Failure to establish and maintain adequate requirements for the health, cleanliness, personal practices, and clothing of personnel if contact between such personnel and product or environment could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(d). For example, an employee working in the (b)(4) was not appropriately dressed on March 26, 2012. Precautions to prevent contamination of equipment or product were not taken. The employee's headgear was not appropriately donned to cover the hair as required.
6. Failure to establish and maintain adequate procedures for identifying product during all stages of receipt, production, distribution, and installation to prevent mix-ups, as required by 21 CFR 820.60. For example, several pallets of devices stored in the finished device warehouse were not properly identified.
7. Failure to use calibration standards for inspection, measuring, and test equipment that are traceable to national or international standards. If national or international standards are not practical or available, then the manufacturer shall use an independent reproducible standard. If no applicable standard exists, then the manufacturer shall establish and maintain an in-house standard, as required by 21 CFR 820.72(b)(1). For example, the temperature calibration records for the (b)(4) dated May 10, 2011, do not show traceability to a certified thermometer.
8. Failure to establish and maintain adequate procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, including quality requirements, that must be met by suppliers, contractors, and consultants. Each manufacturer shall define the type and extent of control to be exercised over the product, services, suppliers, contractors, and consultants, based on the evaluation results, as required by 21 CFR 820.50(a)(2). Specifically, there are no requirements for suppliers' corrective action when nonconformance are found. No procedures or system exists for notifying suppliers of known nonconformances or to ensure corrections and preventive measures are taken by suppliers.
9. Failure to establish and 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). For example, several cases of incoming components in the receiving area were not properly identified in accordance with established procedures. Your firm's procedures state that the status of product cases should be clearly identified as accepted, rejected, or in quarantine.
10. Failure to control labeling and packaging operations to prevent labeling mix-ups, as required by 21 CFR 820.120(d). Specifically, your firm's procedure states that labels are printed as needed for product containers and cases. However, on March 27, 2012, printed labels were found laying on finished cases of (b)(4) The labels in question were not for the (b)(4) products and not under appropriate control in the packaging/labeling area of the warehouse.
11. Failure to establish and maintain adequate procedures to ensure that sampling methods are adequate for their intended use, as required by 21 CFR 820.250(b). Sampling plans, when used, shall be written and based on a valid statistical rationale and the manufacturer shall ensure that, when changes occur, the sampling plans are reviewed. For example:
a. There was no justification or rationale for testing one sample of each packaging material for the test study performed on the (b)(4)
b. There was no evaluation of the limited test results used in the test study on the (b)(4)
12. 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 procedures and operations for the packaging and labeling activities have never been audited.
Given the serious nature of the violations of the Act, the obstetric anesthesia sets; endometrial suction curettes and accessories; vaginal speculums; forceps; cervical, endo-cervical, and endometrial sampling devices; cannulas for endometrial aspiration; devices for vacuum-assisted fetal delivery; uterine manipulators and injectors; devices for sperm collection, artificial insemination, ovum pick-up in gamete intra fallopian transfer, in vitro fertilization, and embryo transfer procedures; and disposable needles for bone and soft tissues biopsy manufactured 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 may take steps to refuse these products, 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 violations described in this letter. We will notify you if your firm's response appears to be adequate, and we may need to re-inspect your firm's facility to verify that the appropriate corrections and/or corrective actions have been made.
Also, 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 actions (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 #308704 when replying. If you have any questions about the contents of this letter, please contact: Debra E. Demeritt at telephone# 301-796-5770 or fax# 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 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.
Steven D. Silverman
Office of Compliance
Center for Devices and