Inspections, Compliance, Enforcement, and Criminal Investigations
Qiagen GmbH 02-Oct-06
Department of Health and Human Services
Public Health Service
2098 Gaither Road
VIA FEDERAL EXPRESS
OCT 2 2006
Mr. Peer M. Schatz
Qiagen Strasse 1
Hilden, Germany D-40742
Dear Mr. Schatz:
During an inspection of your firm located in Hamburg; Germany on July 10, 2006 through July 13, 2006, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures artus® CMV PCR, C. Trachomatis PCR, C. Trachomatis Plus PCR, Parvo B19 PCR, Borrelia PCR, and Malaria PCR Analyte Specific Reagents (ASRs). The Food and Drug Administration has reviewed the Establishment Inspection Report, your Internet site www.qiagendiagnostics.com, and various labeling for these ASRs and has concluded that you market these products as ASRs for sale directly to clinical laboratories and not as components intended to be included as part of a finished, packaged, and labeled device as defined in 21 CFR 820.3(c). Our review has determined that these reagents are medical devices as defined by section 201(h) of the Federal Food, Drug, and Cosmetic Act (Act), 21 U.S.C. § 321(h), 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 are intended to affect the structure or function of the body.
The package inserts for artus® CMV, C. Trachomatis, Parvo B19, Borrelia, and Malaria each states the content as a "Mixture of primers, probes, and enzymes for the specific amplication and detection . . .and for a second heterologous amplification system (Internal Control)". Each of these products is a "multiplex" product, or a product marketed for the detection of more than one chemical substance or ligand. These products do not fall within the scope of 21 CFR 864.4020(a) because that regulation limits ASRs to those reagents that are intended for use in"identification and quantification of an individual chemical substance or ligand in biological specimens." 21 CFR 864.4020(a). The inclusion of internal controls also places your products outside the scope of the ASR rule because that rule is limited to reagents intended for the detection of individual chemical substances or ligands, and does not apply to products that include other components of a test system. In addition, the labeling for each of these products lists additional materials and devices, such as the LightCycler®, ABI PRISM®, and Rotor-Gene™, required for the PCR assay, as well as providing detailed procedures with directions that are unique for the assay - specifically, the quality assurance procedure that describes sample preparation and includes directions for DNA isolation, internal control, preparation of PCR, programming the LightCycler® instruments, and data analysis. Marketing products with instructions for use goes beyond the limits of the regulatory definition of an ASR. Therefore, your products are not ASRs under 21 C.F.R. 864.4020 and require FDA premarket review prior to being marketed.
Accordingly, the artus® CMV PCR, C. Trachomatis PCR, C. Trachomatis Plus PCR, Parvo B19 PCR, Borrelia PCR, and Malaria PCR ASRs are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B), because you do not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. 360j(g). The devices are also misbranded under section 502(o) the Act, 21 U.S.C. 352(o), because you did not notify the agency of your intent to introduce these devices into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. 360(k). For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency. 21 C.F.R. 807.81(b). The kinds of information you need to submit in order to obtain approval or clearance for these devices are available through the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information you submit and decide whether your products may be legally marketed.
You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly correct these violation(s) may result in regulatory action, which may include detaining your devices without physical examination upon entry into the United States until the corrections are completed. Section 801(a) of the Act (21 U.S.C. § 381(a)). Also, U.S. 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. 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.
Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed. If the documentation is not in English, please provide a translation to facilitate our review.
Your response should be sent to James Woods, Deputy Director of Patient Safety and Product Quality, Office of In Vitro Diagnostic Device Evaluation and Safety, 2098 Gaither Road, HFZ-440, Rockville, Maryland 20850. If you have any questions about the content of this letter please contact Tamara Felton at (240)276-0496 x 102.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA.
Steven I. Gutman, M.D., M.B.A.
Office, of In Vitro Diagnostic Device
Evaluation and Safety
Center for Devices and Radiological Health