Inspections, Compliance, Enforcement, and Criminal Investigations
Diamedix Corporation 03-Jun-04
Department of Health and Human Services
Public Health Service
555 Winderley Pl., Ste. 200
RETURN RECEIPT REQUESTED
June 3, 2004
Giorgio D’Urso, President
2140 North Miami Avenue
Miami, Florida 33127-4916
Dear Mr. D’Urso:
During an inspection of your establishment located in Miami, Florida on March 8 - 12, 2004, FDA Investigator Victor Spanioli determined that your firm manufacturers a wide variety of immunology and microbiology ELISA (Enzyme Linked ImmunoSorbent Assay) IVD reagents and analyzers, which can be used manually or in conjunction with the Mago® Plux/Aptus® Automated EIA Analyzers. These products are devices as defined by section 201 (h) of the Federal Food, Drug, and Cosmetic Act (the Act), [21 U.S.C. 321(h)].
The investigator documented significant violations from the Quality System (QS) Regulation, Title 21, Code of Federal Regulations (CFR), part 820. These violations cause the devices you manufacture to be adulterated within the meaning of Section 501 (h) [21 U.S.C. 351 (h)] of the Act.
The investigator noted the following violation of the QS regulations:
Your firm failed to identify the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems as required by 21 CFR 820.100(a)(3). Corrective and Preventive Action Records (CAPAR) were not completed for nonconformities or potential causes of nonconformities requiring investigation, trend analysis, review by management and corrective and preventive action (FDA 483; Item #1). For example, numerous complaints were not documented:
1. Complaint #84, dated 2/19/2003, and #s 172 and 174 dated 4/14/2003 referenced excessive false positives of the Syphilis TREP-CHEK, lot S0002. A CAPAR was not opened as required by SOP: QA 6.0, Corrective and Preventive Action (CAPA) Process.
2. Complaint #s 334, 377, 390, 402, 479 and 516, received between 7/16 and 10/27/2003, describe the negative control index and/or positive controls not meeting specifications for Syphilis TREPCHEK, lot 42003. The contract manufacturer concluded that the root cause of the failures was the kit conjugate; however, no CAPAR(s) were opened and documented.
3. Complaint #511, dated 10/21/2003, describes an increase in false positives for Syphilis TREP-CHEK, lot 71303. The contract manufacturer concluded the root cause of the false positives “was a one time in-process deviation which was corrected by employee training.” A CAPAR was not opened and documented.
4. Complaint #503, dated 10/10/2003, describes excessive false positives for Borrelia burgdorferi IgG/IgM, lot 082K6471 manufactured by [redacted] The [redacted] Service Report summary stated the increased positive rate/inconsistent results could be due to “. . .undissolved particles (Reiters) in the diluent causing the Aptus probe to aspirate inconsistent volume of diluent.” No additional CAPARs were opened for complaints involving lot 082K6471 and related lot 082K6456, which identified complaint #s 320,492, 502, 508, and 532 received between 7/9 and 11/13/2003.
5. Complaint #483, dated 9/29/2003, describes high recoveries for the negative control and low calibrator recovery for anti-Cardiolipin IgG, lot 082K6462 manufactured by [redacted] Diamedix inhouse testing confirmed high recovery for the negative control using both the manual and automated methods. No CAPAR was opened and documented.
6. Complaint #s 448 and 449, dated 9/11/2003, describe high sample recoveries for the APO-TEK Lp(a), lot S1402 manufactured by [redacted] reported that “We were able to confirm the complaint of increased results with sample #s 60-47 to 60-50 and the returned kit from the customer of lot S1402 as reported by the customer.” No CAPAR was opened and documented.
Your response, dated April 9, 2004, is inadequate because it fails to address the existing requirement in SOP QA 6.0 noted under 4. Responsibilities, 4.1, “Any employee subject to the scope of Diamedix Quality Management System is responsible for initiating a CAPAR, if a nonconformance or a potential nonconformance is observed within the quality system.” Your response fails to address SOP QA 6.6, Procedure for Conducting Process and Product Failure Investigations currently in effect, which states under 6.0 that all investigations should be completed within [redacted] days. In addition, your response fails to address the need for trend analysis, review of design controls, review by responsible management, and subsequent CAPA to verify/validate correction.
Your responses, dated April 9, 2004, to FDA 483 Items 2-7 appear adequate. However, you have not attached to your response evidence of implementation of these corrections. In general, your responses appear to be specific spot fixes and do not take a systematic approach to comprehensively cover the corrective and preventive actions. FDA will verify that these responses have been implemented on a systematic basis in its next inspection.
This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and regulations. Federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts.
You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil penalties. Additionally, no premarket submissions for Class III devices to which QS regulation deficiencies are reasonably related will be cleared until the violations have been corrected. Also, no requests for Certificates for Products for Export will be approved until the violations related to the subject devices have been corrected
Please notify this office in writing within fifteen (15) working days of receipt of this letter, of any steps that you are still in the process of taking to correct the noted violations, including (1) the time frames within which the corrections will be completed, (2) any documentation indicating the corrections have been achieved, and (3) an explanation of each step being taken to identify and make corrections to any underlying systems problems necessary to assure that similar violations will not recur.
Your response should be sent to Timothy J. Couzins, Compliance Officer, Food and Drug Administration, 555 Winderley Place, Suite 200, Maitland, Florida 32751, (407) 475-4728.
Director, Florida District