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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Atossa Genetics, Inc. 2/20/13

  

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

Public Health Service
Food and Drug Administration
 
Seattle District
Pacific Region
22215 26th Avenue SE, Suite 210
Bothell, WA 98021
 
Telephone:      425-302-0340
FAX:    425-302-0402

 

February 20, 2013
 
OVERNIGHT DELIVERY
SIGNATURE REQUIRED
 
In reply refer to Warning Letter SEA 13-13
 
Steven C. Quay, MD, Ph.D., FCAP
CEO and President
Atossa Genetics, Inc.
1616 Eastlake Avenue East, Suite 4411
Seattle, Washington 98102
 
WARNING LETTER
 
Dear Dr. Quay:
 
During an inspection of your firm located in Seattle, Washington, on July 16, 2012, through July 25, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Mammary Aspirate Specimen Cytology Test (MASCT) System, and MASCT System Collection Kit.  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 cGMP requirements of the Quality System regulation found under Title 21, Code of Federal Regulations (CFR), Part 820. We received a response from you dated August 6, 2012, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations (FDA 483) that was issued to you. We address the response 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 21 CFR 820.30(a). For example, (b)(4), your firm’s Regulatory Consultant, indicated that you have not established design control procedures for the MASCT System.
 
We reviewed your firm’s response and conclude that it is not adequate.  While a procedure titled SOP-007, Design Control for the MASCT System was submitted in the response, no evidence of implementation or training on this procedure was provided. In addition, you did not provide evidence that you retrospectively reviewed all devices to ensure they had design control procedures in place as required for all devices.
 
2.      Failure to establish and maintain adequate procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). For example, (b)(4), your firm’s Regulatory Consultant, indicated that you have not established procedures for design changes for the MASCT System. You have performed multiple design changes, specifically:
 
a.    You made a design change to a filter of the MASCT System prior to distribution; the only documentation covering the design change is email communication between your firm and the contract manufacturer; and
b.    You are currently performing design changes to the MASCT System device and design verification testing has been performed for these design changes; however, Ms. Deborah H.P. Jae, your firm’s Marketing Director, indicated that no design inputs or outputs were established and no verification procedures were established for these design changes to the MASCT System.
 
We reviewed your firm’s response and conclude that it is not adequate. While a procedure titled SOP-007, Design Control for the MASCT System was submitted in the response, no evidence of implementation or training on this procedure was provided. In addition, you did not provide evidence that you documented the design changes for the change to the filter of the MASCT System nor other changes made to the MASCT System, as required as a correction to this observation. Lastly, you did not provide evidence that you retrospectively reviewed all devices to ensure it implemented design changes made to devices, as required.
 
3.      Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, when asked by the investigator, Mr. (b)(4), your firm’s Regulatory Consultant, indicated that you have not established procedures for corrective and preventive action.
 
We reviewed your firm’s response and conclude that it is not adequate. While a procedure titled SOP-005, Corrective and Preventive Action was submitted in the response, no evidence of implementation or training on this procedure was provided. In addition, you did not provide evidence that you retrospectively reviewed previous corrective actions to ensure they were completed, as required.
 
4.      Failure to maintain adequate complaint files and to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example, when asked by the investigator, Mr. (b)(4), your firm’s Regulatory Consultant, indicated that you have not established complaint handling procedures and that you do not have a formally designated unit for handling complaints. Your firm received a complaint in December 2011 and another in January 2012, concerning thread breakage of the MASCT System funnel; however, the complaints were not maintained in a complaint file.
 
We reviewed your firm’s response and conclude that it is not adequate. While a procedure titled SOP-009, Customer Complaints was submitted in your response, no evidence of implementation or training on this procedure was provided. In addition, you did not provide evidence that you created a complaint file to include all complaints as required as a correction to this observation, nor did you indicate you retrospectively reviewed all complaints to ensure they were received, reviewed and evaluated as required as a corrective action to this observation.
 
5.      Failure to maintain an adequate record of investigation by a formally designated unit when an investigation is made under 21 CFR 820.198, as required by 21 CFR 820.198(e). For example, your firm received a complaint in December 2011, and another in January 2012, concerning thread breakage of the MASCT System funnel; however, the record of investigation for these complaints did not include all required information, such as the exact date a complaint was received, the address and phone number of the complainant, dates and results of the investigation, and correspondence with the complainant. 
 
We reviewed your firm’s response and conclude that it is not adequate. While a procedure titled SOP-009, Customer Complaints was submitted in your response, no evidence of implementation of or training on this procedure was provided. In addition, you did not provide evidence that you documented the record of the investigation of the complaint concerning the breakage of the MASCT System funnel received in December 2011 and January 2012 as required as a correction to this observation. Also, you did not provide evidence that you retrospectively reviewed all other complaints to ensure that the investigations completed were documented as required as a corrective action to this observation.
 
6.      Failure to establish and maintain adequate requirements, including quality requirements, that must be met by suppliers, contractors, and consultants, as required by 21 CFR 820.50(a). For example, your firm contracts (b)(4); however, there is no documentation recording the evaluation and approval of these contractors. When asked by the investigator, (b)(4), your firm’s Regulatory Consultant, indicated that you have not established requirements that must be met by (b)(4).
 
We reviewed your firm’s response and conclude that it is not adequate. While a procedure titled SOP-006, Supplier Evaluation and Monitoring was submitted in your response, no evidence of implementation or training on this procedure was provided. In addition, your firm did not provide evidence that it evaluated (b)(4) as a supplier as a correction to this observation. Also, you did not provide evidence that you retrospectively reviewed all suppliers to ensure they were evaluated, as required.
 
7.      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 21 CFR 820.22. For example, when asked by the investigator, (b)(4), your firm’s Regulatory Consultant, indicated that your firm does not have procedures for quality audits.
 
We reviewed your firm’s response and conclude that it is not adequate. While a procedure titled SOP-004, Internal Quality Audits was submitted in your response, no evidence of implementation or training on this procedure was provided. In addition, your firm did not provide evidence that it conducted a quality audit as required as a corrective action to this observation. Lastly, your firm did not provide evidence that it retrospectively reviewed all quality system procedures to ensure they were documented, as required.
 
8.      Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of 21 CFR 820 and the manufacturer’s established quality policy and objectives, as required by 21 CFR 820.20(c). For example, when asked by the investigator, (b)(4), your firm’s Regulatory Consultant, indicated that your firm does not have procedures for management review.
 
We reviewed your firm’s response and conclude that it is not adequate. While a procedure titled SOP-003, Management Review was submitted in your response, no evidence of implementation or training on this procedure was provided. In addition, your firm did not provide evidence that it conducted a management review as a corrective action, as required.
 
9.      Failure to establish and maintain procedures to ensure that device history records for each batch, lot or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record and the requirements of 21 CFR 820, as required by 21 CFR 820.184. For example, your firm lacks procedures for device history records for the MASCT System. When the investigator requested the device history record for the MASCT System, Ms. Deborah H. P. Jae, your firm’s Marketing Director, indicated that (b)(4) stated it did not maintain records for parts manufactured.
 
We reviewed your firm’s response and conclude that it is not adequate. The response states that SOP-007, Design Control for the MASCT System discusses the content of the device history record; however, this procedure addresses the content of a device history file and not a device history record. In addition, your firm did not provide evidence that it completed a device history record for the MASCT System, nor did your firm provide evidence that it would retrospectively review records for other devices to ensure device history records were documented, as required.
 
10.       Failure to establish a quality plan which defines the quality practices, resources, and activities relevant to devices that are designed and manufactured, as required by 21 CFR 820.20(d). For example, when asked by the investigator,(b)(4), your firm’s Regulatory Consultant, indicated that your firm has not established a quality plan.
 
We reviewed your firm’s response and conclude that it is not adequate. The response states that a Quality Policy has been established and that a Quality Manual will be established by September 7, 2012; however, no documentation was provided to support this response and no mention of a quality plan was discussed in the response.
 
Our inspection also revealed that after the MASCT System device received 510(k) clearance (K030443) a modification to the Nipple Aspirate Fluid (NAF) specimen collection process was made. The premarket notification submission (K030443) included Instructions For Use (IFU) stating to “Wash the collection membrane with fixative solution into the collection vial . . ..” Our inspection revealed your current IFU states “. . . apply one spray of Saccomanno’s Fixative to the collection membrane . . ..”  This change fixes the NAF specimen to the filter paper rather than washing it into a collection vial.   
 
The aforementioned change to the device could significantly affect its safety or effectiveness and requires the submission of a 510(k) to FDA, as required by 21 CFR 807.81(a)(3)(i). We have no record of receiving a 510(k) for this change to your product. Because you do not have marketing clearance from the FDA, marketing the changed product is a violation of the law. In legal terms, the product is adulterated under section 501(f)(1)(B), [21 U.S.C § 351(f)(1)(B)], and misbranded under section 502(o) of the Act, [21 U.S.C. § 352(o)]. Your product is misbranded under the Act because you did not submit a section 510(k) premarket notification, which is required by 21 U.S.C. § 360(k), that shows your device is substantially equivalent to other devices that are legally marketed.  Until you submit a section 510(k) premarket notification and FDA reviews it and notifies you that you may market your device, your product is also adulterated under the Act because the law requires, and you do not have, an approved premarket approval application that shows your device is safe and effective. For a device requiring premarket approval, 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 device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html.  The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.
 
Our inspection, and subsequent review of your websites www.atossagenetics.com and www.nrlbh.com determined that your devices are misbranded under Section 502(a) of the Act [21 U.S.C. 352(a)] and within the meaning of 21 CFR 807.97, in that your websites contain statements that create an impression of official approval of a device due to clearance of a premarket notification submission. 
 
Specifically,
 
  • “. . . Using our patented, FDA-approved Mammary Aspirate Specimen Cytology Test (MASCT) System . . ..” 
  • “. . . FDA has determined, based on clinical trial data, that the MASCT System can be used in the determination and/or differentiation of normal versus premalignant versus malignant cells . . .”
 
Any representation that creates an impression of official approval of a device due to compliance with the premarket notification regulations is misleading.  Your devices were not approved by the FDA, but were determined to be substantially equivalent within the meaning of Section 513(i)(1)(A) of the Act, 21 U.S.C. 360c(i)(1)(A). 
 
In addition, your ForeCYTE test is misbranded under section 502(a) of the Act [21 U.S.C. 352(a)] in that its labeling is false or misleading. Specifically, its labeling contains the following statement:
 
  • “. . . FDA Cleared, clinically proven, and peer reviewed, the ForeCYTE test provides women aged 18 to 65 objective and actionable information to improve their breast health . . .”
 
Your ForeCYTE test was not cleared by FDA. We acknowledge that you modified some of the language on your websites during the inspection, however, your websites still reference “. . . FDA-Cleared . . .” in many instances.
 
Our inspection also revealed that your devices are misbranded under section 502(t)(2) of the Act 21 USC 352 (t)(2), in that your firm failed or refused to furnish material or information respecting the devices that is required by or under section 519 of the Act, 21 USC 360i, and 21 CFR Part 803 – Medical Device Reporting (MDR) Regulation. Significant deviations include, but are not limited to:
 
Failure to develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17.  For example, your firm does not have a MDR procedure.
 
We reviewed your firm’s response and conclude that it is not adequate. Your response did not address the lack of an MDR procedure.
 
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 the 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. Additionally, premarket approval applications for Class III devices to which the Quality System regulation violations 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 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 all violations included in this Warning Letter.
 
Your firm’s response should be sent to: U.S. Food and Drug Administration Seattle District Office, 22215 26th Avenue SE, Suite 210, Bothell, Washington 98021. Refer to the WL SEA 13-13 when replying. If you have any questions about the contents of this letter, please contact: Compliance Officer Brenda L. Reihing at 425-302-0429.
 
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 FDA 483, Inspectional Observations, 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/
Charles M. Breen
District Director
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Warning Letter Company Response

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