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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Interlab S.r.l. 2/28/13

  

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

Public Health Service
Food and Drug Administration
 10903 New Hampshire Avenue
Document Control Room - WO66-G609
Silver Spring, MD 20993-0002 

 

FEB 28 2013
 
 
 WARNING LETTER
 
 
VIA UNITED PARCEL SERVICE
 
Roberto Maggi
President
Interlab S.r.l. 
Via Rina Monti, No. 26
00155 Rome, Italy
 
Dear Mr. Maggi:
 
During an inspection of your firm located in Rome, Italy on October 22, 2012 through October 25, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Class II, non-sterile, Immunofixation Electrophoresis (for Immunoglobulins IgG, IgA, IgM, Kappa and Lambda Immunological) Test using the Interlab G26 v2.0 Instrument in conjunction with Easy Mask antisera application device; Class I, non-sterile, Serum Protein Electrophoresis Test/Kit for the US market. 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 responses from Laura Maggi, Quality System Representative dated October 31, 2012 (Observation 4), November 9, 2012 (general response) and November 13, 2012 (observation 2 &# 3) concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We addressed the 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 to control the design of the device in order to ensure that specified design requirements are met, as required by 21CFR 820.30(a). 
 
For example: the first revision of the firm’s Design Control Procedure for the Immunofixation Electrophoresis Test Kit, Document (b)(4), was established on October 23, 2012. The firm has yet to subject the Immunofixation Electrophoresis Test using Interlab G26 v2.0 Instrument (cleared under 510(k) #k120169 on August 24, 2012) through the design control process in order to ensure that specified design requirements are met. Ms. Laura Maggi, the firm’s Quality System Representative, indicated that the firm has not conducted design controls for the Immunofixation Electrophoresis Test.
 
We reviewed your firm’s response and conclude that it is not adequate.
The response dated November 9, 2012 is not adequate. The responses dated October 3, 2012 and November 13, 2013 did not address this observation. The response is not adequate because: a copy of CAPA #17 was not provided; the firm did not indicate it conducted a retrospective review of all devices to ensure they completed design controls as required; and the firm did not indicate they conducted training on the revised procedures.
 
2.    Failure to ensure that where 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: the firm currently uses the (b)(4), to produce (or mix) the buffer used to manufacture the Immunofixation gel plates. However, the mixing process has not been validated. Ms. Maria Scala Bernalda, the firm’s Production Manager, stated that the firm has not validated the mixing process.
 
We reviewed your firm’s response and conclude that it is not adequate.
The responses dated October 31, 2012; November 9, 2012 and November 13, 2012 are not adequate. The response dated October 31, 2012 did not address this observation. The responses are not adequate because the firm did not provide documentation or evidence of consideration of a systemic corrective action to include a retrospective review of all processes to ensure they were validated as required and to ensure that the same problem does not happen again.  In addition, the firm did not provide evidence that training was conducted on the updated procedure.
 
3.    Failure to establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications where deviations from device specifications could occur as a result of the manufacturing process, as required by 21 CFR 820.70(a).
 
For example: the firms’ Gel Plate Production Procedure for the Immunofixation Kits, Document (b)(4), is incomplete in that:
 
a.    The procedure states that the mixing time required for the dissolution is equal to at least (b)(4). However, it does not require the technician to document the mixing time in the production record (or device history record – DHR). For example DHRs (b)(4).
b.    The firm currently uses the (b)(4), to mix the buffer. However, it does not specify the speed (from 1 to 10) to use for the mixing process.
c.    There is a discrepancy in the firm’s mixing time requirements – (b)(4) in Document (b)(4) and (b)(4) in Form (b)(4).
 
We reviewed your firm’s response and conclude that it is not adequate.
The responses dated October 31, 2012, November 9, 2012 and November 13, 2012 are not adequate. The responses are not adequate because the firm did not indicate that they produced the gel plates as required by the revised procedures to ensure the gel plates met specification. In addition, the firm did not provide evidence that it considered any systemic corrective actions including a retrospective review of all products to ensure they were produced as required and meet specifications.
 
4.    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: the firm’s Non-Conformity and Complaint Management Procedure, document (b)(4), does not require complaints be evaluated to determine whether the complaint should be filed as a Medical Device Report (MDR) to US FDA. A total of (b)(4) complaints (from July 2011 to October, 2012) were reviewed during the inspection. All (b)(4) complaints lacked MDR evaluation. Ms. Laura Maggi, the firm’s Quality representative, indicated that the firm’s current complaint handling procedure does not require complaints to be evaluated for MDR reportability.
 
We reviewed your firm’s response and conclude that it is not adequate.
The response dated November 9, 2012 is not adequate. The responses dated October 31, 2012 and November 13, 2013 did not address this observation. This response is not adequate because the firm did not provide evidence that it retrospectively reviewed all complaints documented after the effective date of the current procedure to ensure they were completed as required.
 
5.    Failure to establish and maintain 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 DMR and the requirements of 21 CFR 820.184, as required by 21 CFR 820.184. 
 
For example: three device history records for 10 reagents from 2012 (pertaining to the Immunofixation gel plates) were selected for review during the inspection, DHR (b)(4), DHR (b)(4), and DHR (b)(4) (correct (b)(4)). The firm failed to use the specified amount of reagents to produce the buffer for the Immunofixation gel plates in all (b)(4) batches.
 
We reviewed your firm’s response and conclude that it is not adequate.
The responses dated October 31, 2012 and November 9, 2012 are not adequate. The response dated November 13, 2013 did not address this observation. The responses are not adequate because the firm did not indicate that it retrospectively reviewed all DHRs to ensure they were documented as required.
 
6.    Failure to establish 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 CFR 820.22. 
 
For example: the firm’s Internal Audit Procedure, Document (b)(4), requires a (b)(4) audit schedule be approved by management. The firm failed to conduct the audits listed on the audit schedule in 2010 and 2011 ((b)(4) audits in 2010 and (b)(4) in 2011; detailed audit area is provided in the EIR).
 
We reviewed your firm’s response and conclude that it is not adequate.
The response dated November 9, 2012 is not adequate. The responses dated October 31, 2012 and November 13, 2013 did not address this observation. The response is not adequate because: a copy of CAPA #17, which was opened to address this deficiency, was not provided; the firm did not provide evidence of implementation of the correction and the corrective action to include evidence that internal audits were conducted for 2012 that were not previously conducted as required and a retrospective review to ensure all audits have been performed as required.
 
Your firm’s responses dated November 16, 2012; November 27, 2012 and December 21, 2012 to the Form FDA 483 (FDA 483) were not reviewed because they were not received within fifteen business days of issuance of the FDA 483. The responses may be evaluated along with any other written material provided in response to the violations cited in this Warning Letter. These include, but are not limited to the violations described in #1, 5 and 6 above.
 
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. 
 
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 #392347 when replying. If you have any questions about the contents of this letter, please contact: James L. Woods, Deputy Director for Patient Safety and Product Quality at 301-796-6225or fax at 301-847-8514.
 
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/                       
Alberto Gutierrez
Director
Office of In Vitro Diagnostic Devices
   And Radiological Health
Center for Devices and
   Radiological Health