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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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THD SpA 3/26/13

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 10903 New Hampshire Avenue
Silver Spring, MD 20993-0002 

 

March 26, 2013
 
WARNING LETTER
 
 
VIA UNITED PARCEL SERVICE
 
Mr. Filippo Bastia
Managing Director and Chief Executive Officer
THD S.p.A.
Via Industria 1
42015 Correggio (RE) Italy
 
Dear Mr. Bastia:
 
During an inspection of your firm located in Correggio, Italy, on November 5, 2012, through November 8, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Rectoscopes, Anescopes, Proctoscopes and Doppler Systems devices.  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 December 12, 2012, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that were issued to your firm. We address these responses 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 receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).
 
For example, your firm’s complaint handling procedure titled Market Surveillance: Notifications and Complaints-PI014 has not been completed and implemented to include requirements that ensure that complaints are evaluated to determine whether the complaint should be filed as a Medical Device Report (MDR).  Additionally, the FDA investigator reviewed (b)(4) complaints and none had documentation of your firm's decision on whether a Medical Device Report should be filed or not.

We have reviewed your response dated December 17, 2012, and conclude that its adequacy cannot be determined at this time. Although your firm has revised its procedure to include complaint handling, MDR and Vigilance Reporting, and Recalls, a retrospective review of previous complaints to determine MDR reportability will not be completed until the end of May, 2013.    

2.    Failure to review and evaluate all complaints to determine whether an investigation is necessary, as required by 21 CFR 820.198(b).
 
For example, your firm’s complaint-handling procedure did not include requirements to ensure that complaints where no investigations were made always included the reason for not investigating the complaint, and the name of the individual responsible for the decision not to investigate.
 
We have reviewed your firm’s response received December 17, 2012, and conclude that its adequacy cannot be determined at this time. Although your firm has revised its procedure to include complaint handling, MDR and Vigilance Reporting and Recalls, a retrospective review of previous complaints to determine MDR reportability will not be completed until the end of May, 2013.  
 
3.    Failure to establish and maintain procedures for implementing corrective and preventive actions, as required by 21 CFR 820.100(a).
 
For example, your firm’s corrective and preventive action procedure did not ensure that all activities conducted were documented. Of the (b)(4) CAPA records reviewed, none of them had all required information documented in the files. Two of the files did not ensure that corrective/preventive actions were verified/validated prior to implementation. The implementation of the corrective/preventive actions were not verified for one of the (b)(4) CAPA files reviewed.
 
We have reviewed your firm’s response received December 17, 2012, and we conclude that it is not adequate. Although your firm has indicated that it issued a revised CAPA procedure on November 16, 2012, the training of personnel on the new procedure and retrospective review of all complaints have not been completed. 
 
4.    Failure to establish and maintain acceptance procedures for verifying the device design, as required by 21 CFR 820.30(f).
 
For example, your firm’s design verification procedures titled Design PIO15 (multiple revisions reviewed) did not include requirements that ensure that the design verification results, including identification of the design and methods, are documented and filed in the design history file. Two of (b)(4) design verification tests reviewed did not include all required documentation including the identification of the design and, in one of the (b)(4) verification tests reviewed, no protocol outlining the methods was approved prior to starting the testing.
 
We have reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
5.    Failure to establish and maintain procedures to ensure that formal documented reviews of the design results are planned and conducted at appropriate stages of the device’s design development. The procedures shall ensure that participants at each design review include representatives of all functions concerned with the design stage being reviewed and an individual who does not have direct responsibility for the design stage being reviewed, as required by 21 CFR 820.30(e).
 
For example, when the investigator reviewed the design review meeting minutes for the final design review prior to release to production, it was noted that no one from production was present at the meeting. None of the (b)(4) design review meeting minutes reviewed included an individual without direct responsibility for the design stage being reviewed.
 
We have reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
6.    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, there was no validation procedure or documentation of process validation activities for the Installation Qualification, Operating Qualification, and Process Qualification for the (b)(4) used in your firm's packaging operations for sterile and non-sterile products.
 
We have reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
7.    Failure to review and evaluate the process and perform revalidation where appropriate, as required by 21 CFR 820.75(c).
 
For example, your firm implemented new parameters in May, 2012, but your firm did not document the revalidation of the (b)(4) of the (b)(4) using the (b)(4).
 
We have reviewed your firm’s response received December 17, 2012, and we conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
8.    Failure to establish and maintain procedures that define the responsibility for review and the authority for the disposition of nonconforming products, as required by 21 CFR 820.90(b)(1).
 
For example, your firm's management of nonconformities procedure PI006 did not include requirements to ensure documentation of the justification for use of nonconforming products and the signature of the individual authorizing the use of nonconforming products. For three of the (b)(4) nonconformance records reviewed where determinations of “use as is” were made, the disposition of nonconforming products was not documented in a manner that could identify and quantify the disposition of the nonconforming products.
 
We have reviewed your firm’s response received December 17, 2012, and we conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
9.    Failure to establish and maintain the requirements, including quality requirements that must be met by suppliers, contractors, and consultants, as required by, 21 CFR 820.50(a).
 
For example, a review of your firm’s 2011 and 2012 audit plans revealed that there was no audit conducted of the contract sterilizer. Also, there were no audits conducted in 2009 and 2010.
 
We reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
10.    Failure to establish and maintain acceptance procedures, where appropriate, to ensure that specified requirements for in-process products are met, as required by 21 CFR 820.80(c).
 
For example, the test results for in process (b)(4) testing of the rectoscopes were not documented.  
 
We reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
11.    Failure to establish and maintain procedures for identifying valid statistical techniques required for establishing, controlling, and verifying the acceptability of process capability and product characteristics, as required by 21 CFR 820.250(a).
 
For example, there were no procedures for identifying valid statistical techniques for sampling of incoming inspections of components for new design product verification or new design validation testing.
 
We reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
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 quality audit procedure did not include requirements that ensure auditors do not have direct responsibility for the matters being audited. Also, your firm’s Quality Manual requires that audits be performed only by management personnel, but it does not include requirements that ensure that the auditor does not have direct responsibility for the matters being audited.
 
Your firm’s procedure states that the time between audits shall not exceed (b)(4), but the investigator noted that there was a (b)(4) time frame between audits, from xx to xx.
 
We have reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
13.    Failure to establish and maintain adequate procedures to ensure that Device History Records (DHRs) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the Device Master Record (DMR), as required by 21 CFR 820.184. 
 
For example, the Evolution device did not have a primary identification label in the DHRs.
 
We have reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.

14.    Failure to establish procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities. Training shall be documented, as required by 21 CFR 820.25(b).

For example, there was no training record for one quality control employee and two assembly operators during a tour of the facility.
 
We have reviewed your firm’s response received December 17, 2012, and conclude that it is not adequate. Your firm did not address this observation in the response submitted.
 
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, Rm 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #392220 when replyingIf you have any questions about the contents of this letter, please contact: Debra Demeritt, at 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 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. 
                                                                
Sincerely yours,
/S/                                                           
Steven D. Silverman
Director
Office of Compliance
Center for Devices and
   Radiological Health