Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
VIA UNITED PARCEL SERVICE
MAY 14, 2012
Via Perotti, 10
25125 Brescia, Italy
Dear Mr. Trivia:
During an inspection of your firm located in Brescia, Italy, on 01/13/2012, through 01/17/2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Universal Transport Media and WASP analysis equipment. 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 Stefania Trevia, Quality Assurance and Regulatory Affairs Manager, dated February 02, 2012, concerning our investigator's observations noted on the Form FDA 483 (FDA 483), List of lnspectional 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 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). For example,
a. A study protocol including acceptance criteria was not approved prior to conducting the performance qualification of the (b)(4)
b. Worst-case conditions, including (b)(4) were not included in the validation studies of the (b)(4) process.
c. Study protocols, including acceptance criteria, were not approved prior to conducting the installation and operational qualification for the equipment (b)(4)
d. There is no documentation that the (b)(4) system used (b)(4) is qualified.
e. There is no documentation that the pressure and balance alarms on the UTM systems are qualified.
f. There is no documentation that the study protocol and acceptance criteria were approved prior to conducting the qualification of the (b)(4)
g. A study protocol including acceptance criteria was not approved prior to conducting the qualification of the (b)(4)
2. Failure to establish and maintain adequate data that clearly describe or reference the specified requirements, including quality requirements, for purchased or otherwise received product and services, as required by 21 CFR 820.50(b). For example, specifications for the (b)(4) from a supplier have not been adequately established.
3. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, procedure (b)(4), does not:
a. describe the procedures for verifying or validating the effectiveness of corrective and preventive actions to ensure that such actions are effective and do not adversely affect the finished device; or
b. require that information relating to quality problems is disseminated to the responsible individuals.
4. Failure to establish and maintain adequate procedures for changes to a specification, method, process, or procedure, as required by 21 CFR 820.70(b). For example, the corrective action for CAPA reports #24/11 and #31/11 addressed the (b)(4). There is no documentation that the change was verified or, where appropriate, validated before the change was implemented.
5. Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.1 98(a). For example, the firm's complaint procedure (b)(4) (rev 01)" does not:
a. address handling of complaints from sources other than e-mail;
b. require complaints to be evaluated for medical device reporting events or
c. require documentation of the complaint investigation or the reason why no investigation was conducted
6. Failure to establish and maintain adequate procedures to control all documents, as required by 21 CFR 820.40. For example, there are no procedures that address the review and approval of external documents with the exception of sterilization and calibration documents. There was no documentation that the (b)(4) study report was reviewed and approved by Copan employees.
7. Failure to establish and maintain adequate procedures to prevent contamination of equipment or product by substances that could reasonably be expected to have an adverse effect on product, as required by 21 CFR 820.70(e). For example, procedure "GR03.1 (b)(4) requires the use of hair nets in the production areas. (b)(4)
We reviewed your firm's response and conclude it is not adequate. For each violation, your firm proposed to revise the applicable standard operating procedure and train employees on the new procedures. However, your firm failed to provide evidence of implementation of the revised procedures and documentation showing that employees have been trained. In addition, evidence of consideration of a systemic corrective action to address these violations was not provided.
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 #303078. If you have any questions about the contents of this letter, please contact: James Woods at 301-796-6225.
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.
Office of In Vitro Diagnostic Device
Evaluation and Safety
Center for Devices and