Inspections, Compliance, Enforcement, and Criminal Investigations
Prince Medical 8/6/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
10903 New Hampshire Avenue
AUG 6, 2012
VIA UNITED PARCEL SERVICE
Jean Claude Prince
64 Rue Gutenberg
Za La Sente DuMoulin
60530 Ercuis, France
Dear Mr. Prince:
During an inspection of your firm located in 60530 Ercuis, France, on March 26, 2012, through March 28, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures sterile and non-sterile diagnostic urodynamic catheters. 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 you dated April 12, 2012, 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 adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example, your firm's complaint procedure, “Non Compliance Treatment Corrective and Preventative Action,” No.5034, Rev 15-Rev 20, dated June 01, 2009 – February 09, 2012, does not adequately define a complaint or the process of handling complaints as required. Of the 11 complaints reviewed, none were evaluated for Medical Device Reporting (MDR) reportability, and the date the complaints were received was not clearly documented.
We reviewed your firm’s response and conclude that it is not adequate. Your firm plans to correct the deficiencies, but did not indicate that it would investigate the 11 complaints to see if they were reportable as MDR events. Your firm also did not indicate that it would review all other complaints to see if any should have been reported as MDR events. No documentation of investigations, verification of implementations of the changes, or training was submitted in the response for FDA to review.
2. Failure to adequately review and evaluate all complaints to determine whether an investigation is necessary and to maintain an adequate record that includes the reason no investigation was made and the name of the individual responsible for the decision not to investigate, as required by 21 CFR 820.198(b). For example, complaint number 11R340, which reported a problem with a blocked catheter, was not investigated. Also, complaint number 11R360, which documents a blocked catheter lumen tube, was not investigated. The complaints indicated that no investigation was conducted because the device was not returned, and there was no record of who made the decision to not investigate.
We reviewed your firm’s response and conclude that it is not adequate. Your firm plans to correct the deficiency by modifying its “5034/J” form to include: (b)(4). No documentation of investigations, verification of implementations of the changes, or training has been submitted to the FDA for review.
3. Failure to maintain an adequate record of the investigation by the formally designated unit identified in 21 CFR 820.198(a) when an investigation is made, as required by 21 CFR 820.198(e). For example, your firm's procedure does not require that complaint investigations include:
a. Evaluation to determine whether the complaint represents an event that is required to be reported to FDA (MDR reportable);
b. Evaluation of all complaints to determine whether an investigation is necessary;
c. Any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications;
d. in cases where a complaint is not investigated, the reason that no investigation was made and the name of the individual responsible for the decision not to investigate;
e. The date that the complaint was received;
f. The name, address, and phone number of the complainant;
g. Any reply to the complainant; and
h. Uniform and timely complaint processing.
We reviewed your firm’s response and conclude that it is not adequate. Your firm plans to correct the deficiency, but did not indicate that it would revise its complaint procedures to include information from the investigation record. Your firm also did not indicate that it would review all investigation records to determine if required information was documented. No documentation of investigations, verification of implementations of the changes, or training has been submitted to the FDA for review.
4. Failure to establish and maintain adequate procedures for the identification, documentation, validation or, where appropriate, verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). For example:
A. Product Design procedure No.5040, rev 10 and rev 11, dated February 03, 2009, and May 19, 2009, does not include adequate requirements for the identification, documentation, validation/verification, review, and approval of design changes before their implementation.
B. Your firm lacks change control documents for the implemented design change of the (b)(4). Your firm’s required Product Life Form for design changes lacks an approval signature and date of approval of this change. In addition, this design change lacked design review and verification.
We reviewed your firm’s response and conclude that it is not adequate. Your response lists several changes to its Design Procedure to aid in correcting the deficiencies. However, your firm did not indicate that it had updated the design change of the (b)(4) by completing the required design change activities pertaining to this change. Your firm also did not indicate that it would review all other design changes to ensure that they were completed as required. No documentation or implementation of design change or training on the revised procedure has been submitted to the FDA for review.
5. 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 procedures, as required by 21 CFR 820.75(a). For example, your firm did not adequately define procedures or approve the clean room validation plan. Specifically:
A. Clean room particle validation Operating Mode No.3030 (Comptage de Particules), dated March19, 2012, contained obsolete plans for test locations in clean rooms 13 and 19. Your firm conducted a clean room particle validation in clean rooms 13, 19, and 22 on March 15, 2012, and March16, 2012. The validation testing was conducted using a validation plan that was not yet approved. The plan was not approved until March 20, 2012.
B. Clean room validation plan Model No. 3030 (Comptage de Particules), dated March 23, 2008, did not contain any plan for the test locations in clean rooms 13, 19, and 22. Your firm conducted a clean rooms particle validation in clean rooms 13, 19, and 22 on September 29, 2011, and March 30, 2011. The validation testing was conducted using an old clean room validation plan that did not contain the updated test locations for the rooms being validated.
We reviewed your firm’s response and conclude that it is not adequate. Your firm is in the process of updating all its facility validations and implementing a revalidation schedule. However, your firm did not indicate that it would review all other validation activities to ensure that they were completed and documented. No documentation of implementation of the changes or training on the revised procedures has been submitted to the FDA for review.
Our inspection also revealed that your firm’s sterile and non-sterile diagnostic urodynamic catheters 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. Significant violations include, but are not limited to, the following:
Failure to develop, maintain, and implement MDR procedures, as required by 21 CFR 803.17. For example, your firm failed to develop, maintain, and implement written MDR procedures. Upon request by the investigator, your firm’s CEO, Deputy Quality Manager, and Quality Administrator that no procedure for MDR existed and that they were unaware that the FDA had a procedure or requirement for adverse event reporting.
The adequacy of your firm’s response cannot be determined at this time.
Your firm submitted a revision of its MDR procedure. However, your firm, failed to submit documentation to support the implementation of the new procedures and documentation showing that employees were trained on the new procedures. Additionally, your firm failed to provide documentation of a systemic corrective action to address the observation.
A follow-up inspection will be required to assure that corrections and/or corrective actions are adequate.
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, Room 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case number 317559 when replying. If you have any questions about the contents of this letter, please contact: Debra E. Demeritt at 301-796-5770.
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