- Multimedical 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
FEB 13, 2015
VIA UNITED PARCEL SERVICE
Via G Rossa, 71
Zona Ind. Gerbolina
46019 Viadana MN
During an inspection of your firm located at Via G Rossa, 71, Zona Ind. Gerbolina, Viadana, Italy, on October 20, 2014, through October 23, 2014, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures intravenous (I.V.) infusion sets, infusion needles, hemodialysis blood lines, blood transfusion sets, intravascular extension lines and accessories for infusion. 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 a response from Alessandra Cesari, Director of Quality, dated November 11, 2014, 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 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:
a. Your firm’s corrective and preventive action (CAPA) procedure does not:
i. Require analyzing sources of quality data to identify existing and potential causes of nonconforming products or other quality problems.
ii. Require appropriate statistical methodology to be employed where necessary to detect recurring quality problems.
iii. Include requirements for verifying or validating corrective and preventive action to ensure that such action does not adversely affect the finished device.
b. Your firm’s finished product release specification for residual ethylene oxide (EtO) following degassing is (b)(4). However, your firm’s complaint trending indicates that EtO degassing issues are contributing to (b)(4) EtO residue on sterilized products. Your firm has not evaluated this quality issue to determine if corrective or preventive actions were necessary.
We reviewed your firm’s response and conclude that it is not adequate. Your firm plans to review quality system data, including trends for nonconformances, past CAPAs, and results of bioburden, and implement necessary corrective actions. Your firm submitted a CAPA procedure, PSQ12/A4 Em 00 Rev 01; however, this procedure does not address the above procedural deficiencies. Also, your firm did not evaluate the risk associated with devices that may have been released with unacceptable EtO residues.
2. Failure to establish and maintain procedures to ensure that all purchased or otherwise received products and services conform to specified requirements, as required by 21 CFR 820.50. For example:
a. Your firm’s quality audit procedure requires an audit for critical suppliers be conducted at least once every three years. However, your firm’s critical suppliers of raw materials and services have not been audited in more than three years.
b. Your firm’s written contract with its sub-assembly contract manufacturer does not require the contract manufacturer to notify your firm of any changes in the products or services which may affect the quality of a finished device.
We reviewed your firm’s response and conclude that it is not adequate. Your firm did not review its current supplier qualification records to evaluate whether any existing or potential deficiencies may have resulted in nonconforming products. Also, your firm did not demonstrate that supplier audits have been completed. Additionally, your firm did not review supplier agreements to collect information on changes made without a notification, and evaluate how those changes could have impacted product quality.
3. Failure to validate computer software for its intended use according to an established protocol when computers or automated data processing systems are used as part of production or the quality system, as required by 21 CFR 820.70(i).
For example, your firm installed (b)(4) in 2007, but has not validated the software for its intended uses.
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that it will notify its software supplier to implement software system validation. However, your firm did not provide specific information on how the software will be validated, such as the protocols and procedures that will be used for validation. Your firm did not indicate how it will ensure that the software requirements are met.
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 (MDR). Significant violations include, but are not limited to, the following:
4. Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17(a)(1). For example, your firm’s MDR procedure does not:
a. Establish 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). For example, there are missing definitions of what your firm will consider to be a reportable event under 21 CFR Part 803. The exclusion of definitions from 21 CFR 803.3 for the terms “become aware,” “caused or contributed,” “MDR reportable event,” and “serious injury,” and the definition for the term “reasonably suggests,” found in 21 CFR 803.20(c)(1) 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. Establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
i. Instructions for how to obtain and complete the FDA 3500A form.
ii. The circumstances under which your firm must submit supplemental reports and the requirements for such reports.
iii. Although the procedure includes references to 30 day reports, it does not specify calendar days.
c. Describe how your firm will address documentation and record-keeping requirements, including:
i. Documentation of adverse event related information maintained as MDR event files.
ii. Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s revised procedure does not address the procedural deficiencies listed above.
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:
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
Given the serious nature of the violations of the Act, the devices manufactured by your firm, including I.V. infusion sets, infusion needles, hemodialysis blood lines, blood transfusion sets, intravascular extension lines and accessories for infusion, 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 violations described in this letter. We will notify you regarding the adequacy of your firm’s response and the 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.
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 2622, 10903 New Hampshire Ave., Silver Spring, MD 20993.Refer to CMS case #444772 when replying. If you have any questions about the contents of this letter, please contact: Daniel Walter, Chief, Foreign Enforcement Branch, at +1 (301) 796-5587, or fax +1 (301) 847-8139.
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.
Jan B. Welch, MHS, MT (ASCP) SBB
Office of Compliance
Center for Devices and