Inspections, Compliance, Enforcement, and Criminal Investigations
International Immuno-Diagnostics 9/14/11
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
San Francisco District
1431 Harbor Bay Parkway
Alameda, CA 94501-7070
Telephone (510) 337-6700
September 14, 2011
1155 Chess Drive, #121
Foster City, California 94404
Dear Ms. Justice:
During an inspection of your firm located in Foster City, California on December 8, 2010 through January 3, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures in-vitro diagnostic reagents (IVSDs). 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 are intended to affect the structure or function of the body.
This inspection revealed that these devices 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). These 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 them 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 CFR 807.81(b)] The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the, information you submit and decide whether your product may be legally marketed.
Our inspection revealed that you are marketing your IVDs as "For Research Use Only" (RUO). Under 21 CFR 809.10(c)(2)(i), IVD products intended only for research use are exempt from the IVD labeling requirements at section 809.10(a) and (b) if the product is in the laboratory research phase of development, is not represented as an effective in vitro diagnostic product, and is labeled: "For research use only. Not for use in diagnostic procedures." Any product that is intended for use in a clinical investigation or clinical diagnostic use outside an investigation (for example, in clinical diagnosis) should not be labeled RUO.1
Even though your device is labeled RUG, you are labeling it and promoting it for nonresearch clinical diagnosis without clearance or approval in violation of the Act. For example:
1. Thyroid Stimulating Hormone (TSH) Enzyme Immunoassay (EIA) Test Kit
Your TSH product insert identifies it for "For Research Use Only Not For Use in Diagnostic Procedures." However, the product states that it is intended for "the quantitative determination of the thyroid stimulating hormone (TSH) concentration in human serum." Additionally, in the "Introduction" section your product insert states, "[t]he determination of serum or plasma levels of thyroid stimulating hormone (TSH) is recognized as a method in the detection of primary and secondary hypothyroidism." Under this same section it also reads, "[t]he use of a monoclonal antibody in the TSH EIA test eliminates this interference, which could result in falsely elevated TSH values in either menopausal or pregnant females-a population whose evaluation of thyroid status is clinically significant." These statements suggest the clinical utility of the device and instruct clinicians on the use of this device to detect and diagnose disease. Also, the TSH EIA is listed in your product catalog under EIA Diagnostic Tests. These are diagnostic claims that indicate that the device is intended for clinical in vitro diagnostic use, and not for research use only.
2. Hepatitis Delta Virus (HDV Ab) Test Kit
Your HDV Ab product insert identifies it "For Research Use Only Not For Use In Diagnostic Procedures." However, language in the product insert indicates that the device is intended for the determination of Hepatitis Delta Virus (HDV Ab) concentration in human serum and plasma. For example:
The "Introduction" section of your product insert states, "[i]nfection by HDV occurs in the presence of acute or chronic HBV infection. When acute delta and acute HBV simultaneously occur, the illness becomes severe and clinical and biochemical features may be indistinguishable for those of HBV infection alone."
"...The determination of HDV specific serological markers (HDV Ag, HDV Ab, HDV IgM and HDV IgG) represents in these cases an important tool to the clinician for the classification of the etiological agent, for the follow up of infected samples and their treatment. The detection of HDV total antibodies allows the classification of the illness and the monitoring of the seroconversion event." Also, the HDV Ab device is listed in your product catalog under EIA Diagnostic Tests. These statements suggest the clinical utility of the device and instruct clinicians on the use of this device to detect and diagnose disease. These are diagnostic claims ..that indicate that the device is intended for in clinical vitro diagnostic use, and not for research use only as claimed by the firm.
In addition, section 510 of the Act (21 U.S.C. § 360) requires manufacturers of medical devices. to annually register with the FDA. In September 2007, section 510 of the Act was amended by the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-85) to require domestic and foreign device establishments to submit their annual establishment registration and device listing information to FDA by electronic means (section 510(p) of the Act (21 U.S.C. 360(p))) during the period beginning October 1st and ending December 31st of each year, and to pay an annual establishment registration fee (section 737(13) and 738(a)(3) of the Act (21 U.S.C. 379i(13) and 379j(a)(3)). Our records indicate that your firm has not fulfilled annual registration and listing requirements for fiscal year 2011. Therefore, all of your firm's devices are misbranded within the meaning of section 502(o) of the Act (21 U.S.C. § 352(o)), in that the devices were manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under section 510 (21 U.S.C. § 360) and were not included in a list required by section 510(j) (21 U.S.C. § 360(j)).
A follow up inspection will be required to assure that corrections and/or corrective actions are adequate. Please be aware that you are required to comply with the Quality System regulation at 21 CFR Part 820.
FDA requests that International Immuno-Diagnostics immediately cease marketing, promoting, and distributing all in vitro diagnostic products that require PMA approval or 510(k) clearance and do not have FDA approval or clearance. The adequacy of your corrective actions will be evaluated during our next inspection.
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations 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 money penalties. 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. 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 15 working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, which may include notification of your current and past customers. Your response should also include 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.
Additionally in your response, please indicate what you plan to do with existing stock and products in the field that have been previously shipped and are still in stock for which you lack PMA/IDE approval or 510(k) Clearance to market.
Your response should be sent to:
Darlene B. Almogela
Director of Compliance
1431 Harbor Bay Parkway
Alameda, California 94052
Refer to the Unique Identification Number (CMS case 161892) when replying.
If you have any questions about the content of this letter please contact Mr. Lawton W. Lum, Compliance Officer at (510) 337-6792.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. It is your responsibility to assure you obtain the necessary premarket clearance or premarket approval for the intended uses of all of your devices as defined by 21 CFR 801.4. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form FDA"483, issued at the close of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.
Barbara J. Cassens
1 For more information see "Draft Guidance for Industry and FDA Staff-Commercially Distributed In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only: Frequently Asked Questions, available at: http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm253307.htm.