Inspections, Compliance, Enforcement, and Criminal Investigations

Gold Standard Diagnostics 4/25/14

  

Department of Health and Human Services logoDepartment 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 

 

WARNING LETTER
 
April 25, 2014
 
VIA UNITED PARCEL SERVICE
Signature Required
 
John M. Griffiths, Chief Executive Officer
Gold Standard Diagnostics, Inc.
2851 Spafford St, Suite A
Davis, CA 95618-6811
 
Dear Mr. Griffiths:
 
During an inspection of your firm located in Davis, CA on November 19 through December 20, 2013, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Gold Standard Diagnostics test kits for the detection of infectious pathogens, such as Brucella abortis, Brucella melitensis, Brucella suis (the causative agents of brucellosis), and Influenza A virus  (the causative agents of viral A flu), Paramyxoviradae rubulavirus - Mumps virus (the causative agent of Mumps), Paramyxoviradae morbillivirus - Measles virus (the causative agent of Measles), and Toxocara canis (the causative agent of Ocular Larva Migrans and Viseral Larva Migrans). You also are the initial importer and distributor of the Savyon Diagnostics test kit for Bordetella pertussis (the causative agent of Whooping Cough).  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 any function of the body. 
 
PMA/PMN/IDE
Our inspection revealed that the The Gold Standard Diagnostic Adenovirus IgA (ELISA); Adenovirus IgG/IgM (ELISA); Aspergillus fumigatus IgA, IgG, IgM (ELISA); Bordetella pertussis IgA / IgM (ELISA); Bordetella pertussis IgG (ELISA); Bordetella pertussis LINE IgA +catACT LINE IgA (Blots); Bordetella pertussis LINE IgG +catACT LINE IgA (Blots); Brucella IgA Set (ELISA); Brucella IgG (ELISA); Brucella IgM (ELISA); Candida albicans IgA (ELISA); Candida albicans IgG/IgM (ELISA); Ehrlichia chaffeensis IgG Ab Kit (IFA); Francisella tularensis IgG, IgM (ELISA); Influenza A IgA (ELISA); Influenza A IgG/IgM (ELISA); Influenza B IgA (ELISA); Influenza B IgG/IgM (ELISA); Leptospira IgG, IgM (ELISA); Measles IgG (ELISA); Measles IgM (ELISA); Mumps IgM (ELISA); Mumps IgM (ELISA); Mumps IgG/IgM (ELISA); Mycoplasma hominis IgG (ELISA); Mycoplasma pneumoniae IgA Set (ELISA); Mycoplasma pneumoniae IgG/IgM (ELISA); Mycoplasma pneumoniae WB IgA, IgG, IgM (Blots); Parainfluenza IgA/IgG/IgM (ELISA); Pertussis Toxin IgA (ELISA); Pertussis Toxin IgG (ELISA); RSV IgA Set (ELISA); RSV IgG/IgM (ELISA); Typhus Group Rickettsia IgG-Spotted Fever (ELISA); Immco Rheumatoid Factor IgA; Immco Rheumatoid Factor IgG; Diamedix Anti-Thyroid Autoantibodies and 25-OH Vitamin D, Total EIA assay devices to be used with the Thunderbolt or other analyzers are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have approved applications for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or approved applications for investigational device exemptions under section 520(g) of the Act, 21 U.S.C. § 360j(g). These devices are also misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because your firm did not notify the Agency of its intent to introduce the devices into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k). 
 
For a device requiring a PMA, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the Agency, 21 CFR 807.81(b).  The kind of information that your firm needs to submit in order to obtain approval or clearance for the devices is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the products may be legally marketed.
  
Quality System
This inspection also 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 Napoleon Monce, Management Representative dated January 8, 2014 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
 
1.    Failure to establish procedures for design changes as required by 21 CFR 820.30(i). For example, your design and development procedure does not address software changes, or describe how they will be defined, documented, or implemented. You do not describe the types of changes that require software verification or validation.  In response to Complaint # CC0159 you made changes to the Thunderbolt GUI software. You were unable to provide documentation to show the verification or validation of this software change when our investigator asked you for it.
 
2.    Failure to establish requirements that must be met by suppliers as required by 21 CFR 820.50(a). For example, you have no documentation of the design responsibilities your Thunderbolt analyzer software supplier (supplier “A”) must meet and there is no documentation that you or your supplier have validated or verified the analyzer’s software; and according to your management representative, you evaluated supplier “B” solely on years of doing business with them and executive management knows them. Supplier “B” provides reagents, antigens, and antigen coated plate components for your infectious disease devices.
 
3.    Failure to perform a risk analysis as required by 21 CFR 820.30(g). For example, our investigator asked you for and you were unable to produce a risk analysis for the following in vitro diagnostic kits you manufacture: Brucella IgM, Borrelia burgorferi B31 IgG and IgM, and Entamoeba histolytica IgG; and you failed to mitigate the risk of patient misdiagnosis in your Thunderbolt Risk Analysis. Your Thunderbolt Risk Analysis Summary, RMP-0001-3 requires items (b)(4) to have control measures to reduce the probability of occurrence; however, you have assigned a (b)(4) to the general “Operational” hazard that may lead to patient misdiagnosis and have not mitigated the hazard.
 
Medical Device Reporting
Additionally your devices are misbranded within the meaning of section 502(t)(2) [21 U.S.C. § 352(t)(2)], in that the your firm failed or refused to furnish material or information regarding the devices that is required by or under Section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant deviations include, but are not limited to:
 
Failure of your firm to adequately develop, maintain and implement written MDR procedures as required by 21 CFR 803.17. For example, the MDR procedure titled “Medical Device Reporting, QSP-803, Rev A” dated September 1, 2012, revealed the following deficiencies:
 
1.    QSP-803, Rev A does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example: There are no definitions of what your firm will consider to be a reportable event under 21 CFR Part 803. The exclusion of definitions from 21 CFR 803.3 for the terms “become aware,” “caused or contributed,” “malfunction,” “MDR reportable event,” and “serious injury,” and definitions for the terms “reasonably known” and “reasonably suggests,” found respectively in 21 CFR 803.50(b) and 803.20(c)(1) from the procedure, may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
 
2.    QSP-803, Rev A does not establish internal systems that provide for a standardized review process to determine when an event meets the criteria for reporting under this part. For example:
 
a.    There are no instructions for conducting a complete investigation of each event and evaluating the cause of the event. 
 
b.    There are no instructions for how the firm will evaluate information about an event to make MDR reportability determinations in a timely manner.
 
3.    QSP-803, Rev A does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
 
a.    Instructions for how to obtain and complete the FDA 3500A form.
 
b.    The circumstances under which your firm must submit 30 day, supplemental or follow-up, and 5 day reports and the requirements for such reports.
 
c.    How your firm will submit all information reasonably known to it for each event.
 
d.    Does not include the address for where to submit MDR reports: FDA, CDRH, Medical Device Reporting, P. O. Box 3002, Rockville, MD 20847-3002.
 
4.    QSP-803, Rev A does not describe how the firm will address documentation and record-keeping requirements, including:
 
a.    Information that was evaluated to determine if an event was reportable.
 
b.    Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable.
 
c.    Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
 
Review of your firm’s response dated January 29, 2014, revealed that the response it is not adequate. Your firm’s revised MDR procedure titled “Medical Device Reporting, QSP-803, Rev B”, dated January 10, 2014, found the following inadequacies:
 
1. QSP-803, Rev B, does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example:
 
a.   The procedure omits the definition from 21 CFR 803.3 for the term “caused or contributed,” and definitions for the terms “reasonably known” and “reasonably suggests,” found respectively in 21 CFR 803.50(b) and 803.20(c)(1). The exclusion of the definitions for these terms from the procedure may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
 
b.   The definitions for the terms “becomes aware” and “MDR reportable event” are not consistent with the definitions of the terms found in 21 CFR 803.3, and will not allow your firm to correctly identify complaints as reportable events.
 
2. QSP-803, Rev B, does not establish internal systems that provide for a standardized review process to determine when an event meets the criteria for reporting under this part. For example: Although the procedure includes instructions for how your firm will evaluate information about an event to make MDR reportability determinations, it fails to include instructions for making determinations in a timely manner.
 
3. QSP-803, Rev B, does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
 
a.   Instructions for how to obtain and complete the FDA 3500A form. 
 
b.   The circumstances under which your firm must submit 30 day, supplemental or follow-up and 5 day reports, and the requirements for such reports.
 
c.   Although the procedure includes a reference to 30 day reports, it does not specify calendar days as the reporting timeframe.  
 
d.   How your firm will submit all information reasonably known to it for each event.
 
e.   The procedure does not include the address for where to submit MDR reports: FDA, CDRH, Medical Device Reporting, P. O. Box 3002, Rockville, MD 20847-3002.
 
4. QSP-803, Rev B, does not describe how your firm will address documentation and record-keeping requirements, including systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
 
If your firm wishes to submit MDR reports via electronic submission it can follow the directions stated at the following URL: http://www.fda.gov/ForIndustry/FDAeSubmitter/ucm107903.htm
 
If your firm wishes to discuss MDR reportability criteria or to schedule further communications, it may contact the Reportability Review Team by email at ReportabilityReviewTeam@fda.hhs.gov.    
 
Your firm 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 FDA without further notice.  These actions include, but are not limited to, seizure, injunction, and civil money penalties.  Also, 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.  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, as well as 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 actions (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. Your firm’s response should be comprehensive and address the violations included in this Warning Letter.
 
This inspection also revealed that the methods used in, or the facilities or controls used for, manufacture, packing, storage, or installation of the devices are not in conformity with the current good manufacturing practice requirements of the Quality System regulations found at 21 CFR Part 820.  The specific deficiencies were noted on a Form FDA-483, Inspectional Observations issued to you at the conclusion of the inspection. We have received your response dated January 8, 2014.  We will evaluate their adequacy and effectiveness during a follow-up inspection.
 
Your firm’s response should be sent to: Lawton W. Lum, Director of Compliance, 1431 Harbor Bay Parkway, Alameda, CA 94502.  Refer to the Unique Identification Number 419704 when replying. If you have any questions about the contents of this letter, please contact: Sergio Chavez, Compliance Officer at (510) 337-6886 or (510) 337-6703 fax.
 
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,
/S/                                                           
Kathleen Lewis, J.D.
District Director

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