Inspections, Compliance, Enforcement, and Criminal Investigations
Mainline Technology, Inc 1/23/09
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
300 River Place
Detroit, MI 48207
RETURN RECEIPT REQUESTED
January 23, 2009
Martha I. Mazurek
President & CEO
Mainline Technology, Inc.
3985 Research Park Drive
Ann Arbor, Michigan 49108-2282
Dear Ms. Mazurek:
During an inspection of your firm located in Ann Arbor, MI on July 15, 2008 through August 8, 2008, investigator(s) from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Mainline Confirms Strep A, Mainline Confirms Strep A Dots, FYI hCG Urine One-step Pregnancy Test, Mainline Confirms hCG One-step Pregnancy Test, Mainline Confirms III hCG One-Strep Pregnancy Test, and Mainline hCG Accuracy Check pos+ and neg- controls. 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.
Our 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 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 (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. Title 21, Code of Federal Regulations (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 also revealed that your Mainline Confirms Strep A device is misbranded within the meaning of section 502(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360(i), and 21 CFR Part 806 -Reports of Corrections and Removals regulation.
Specifically, during this inspection, it was determined that you had conducted a correction to remedy your manufacture and distribution of certain lots of the Mainline Confirms Strep A test with an incorrect tip, which presented the potential for false positive results. Instructing your customers to either return the product so that the tip could be replaced or use more drops than the number stated in the approved instructions meets the definition of a correction as defined at 21 CFR 806.2(d). This correction is reportable under 21 CFR 806.10(a)(2) because it was initiated "to remedy a violation of the Act caused by the device which may present a risk to health." A risk to health includes situations where "the use of, or exposure to, the product may cause temporary or medically reversible adverse health consequences, or an outcome where the probability of serious adverse health consequences is remote." 21 CFR 806.2(j)(2). Since false positive strep A results may cause adverse health consequences, such as those resulting from the inappropriate use of antibiotic therapy, failure to report the correction described to the FDA within 10 working days after it was initiated violates 21 CFR 806.10(b).
The above-referenced inspection also revealed that these devices are adulterated within the meaning of Section 501(h) of the Federal Food, Drug, and Cosmetic Act 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 conformance with the current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation, as specified in 21 CFR Part 820. Significant deviations include, but are not limited to, the following:
1. 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 Part 820 and the manufacturer's established quality policy and objectives, as required by 21 CFR 820.20(c). Specifically, there is no evidence that management reviews have been conducted. [See inspectional observation 2.]
2. Failure to establish procedures for, and to conduct, quality audits to assure that your firm's 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. Specifically, there is no evidence that you have established quality audit procedures or that quality audits have been performed. [See inspectional observation 3.]
3. Failure to ensure that personnel are adequately trained to perform their assigned functions and to document training, as required by 21 CFR 820.25(b). Specifically, employees involved in the manufacturing, packaging, testing, shipping, and complaint handling of in vitro reagents have not been trained in current Good Manufacturing Practice or the QS regulation, and you were able to provide documentation of any type of training for only one of your current employees. [See inspectional observation 18.]
4. Failure to establish and follow document approval, distribution and change procedures, as required by 21 CFR 820.40. For example, procedures on how to control approval, distribution, and changes to device master records (DMRs), specifications, device history records (DHRs) and labeling for your strep A and hCG in vitro diagnostics were not available and documents not signed as approved for use were being used in product manufacturing and finished product testing locations during this inspection. [See inspectional observations 16 and 17.]
5. Failure to establish procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. For example, quality requirements to be met by your contract manufacturer of your strep A and hCG in vitro diagnostics have not been defined or documented. [See inspectional observation 5.]
6. Failure to develop, conduct, control, and monitor production processes to ensure that your devices conform to their specifications, as required by 21 CFR 820.70. For example, you do not have any established cleaning procedures for the equipment used in the production of strep A and hCG in vitro diagnostics. [See inspectional observation 6.]
7. Failure to ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purposes and is capable of producing valid results, as required by 21 CFR 820.72 (a). Your firm has no procedures to ensure that equipment is routinely calibrated, inspected, checked and maintained. For example, procedures for calibration, inspection, checks and maintenance of your firm's digital scales, autoclave and spectrophotometer used in the manufacture and testing of your strep A and hCG in vitro diagnostics were not available. [See inspectional observation 11.]
8. Failure to validate with a high degree of assurance and approve according to established procedures a process whose results cannot be fully verified by subsequent inspection and test, and failure to document such validation activities and results, as required by 21 CFR 820.75(a). For example, there is no documentation of validation of your firm's manufacturing process, cleaning operations, software calculations or filling operations for your strep A and hCG in vitro diagnostics. [See inspectional observation 9.]
9. Failure to document that incoming product has been inspected, tested, or otherwise verified as conforming to specified requirements, as required by 21 CFR 820.80(b). For example, there is no documentation of acceptance activities for incoming reagents, reagent bottles, bottle droppers, bottle caps, or labeling for your strep A and hCG in vitro diagnostics. [See inspectional observation 13.]
10. Failure to establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, and to hold finished devices in quarantine until all activities required by the DMR are completed, as required by 21 CFR 820.80(d). Specifically, entire lots of your strep A and hCG in vitro diagnostics were tested and released after the first day of assembly/production before all activities required in the DMR had been completed. For example, the following lots were released prior to completion of all activities required in the DMR: Mainline Confirms Strep A, lot 94610; Mainline confirms DOTS Strep A, lot 92720; Mainline confirms III hCG serum/urine, lot 96380 and Mainline Maxie pregnancy test urine hCG, lot 418F30. [See inspectional observation 7.]
11. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100. Specifically, no corrective and preventive action procedures were available during this inspection. [See inspectional observation 15.]
12. Failure to establish and maintain procedures to control labeling activities to assure that a designated individual has examined labeling for accuracy including, where applicable, the correct expiration date, control number, storage instructions, handling instructions, and any additional processing instructions prior to labeling release for storage or use, as required by 21 CFR 820.120(b). For example, the DHR does not include a date or signature of a person who examined and approved the expiration date and lot numbers on your labels for your Strep A and hCG in vitro diagnostics. [See inspection observation 10.]
13. Failure to document the label and labeling used for each production lot in the device history record, as required by 21 CFR 820.120(d). For example, the lot code and expiration labeling for the Strep A and hCG pregnancy screening test kits are not recorded in the DHRs. [See inspectional observation 8.]
14. Failure to maintain DMRs that include, or refer to the location of, device specifications, as required by 21 CFR 820.181(a). For example, the DMRs for your strep A and hCG in vitro diagnostics do not include or refer to the locations of all specifications for all reagents, bottles, dropper tip caps or dropper tips. [See inspectional observation 14.]
15. Failure to establish and maintain a design history file (DHF) for each type of device, as required by 21 CFR 820.30(j). For example, you have failed to provide a DHF for any of the devices that your firm manufactures. [See inspectional observation 12.]
16. Failure to maintain complaint files, and to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198. For example, you stated that you stopped documenting complaints over a year ago, and there is no evidence that complaints 02-05-037, 02-06-004 and 02- 6-023 were reviewed or evaluated. [See inspectional observation 4.]
We received a response from you dated August 15, 2008, concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. This response states that you intend to discontinue manufacturing Mainline Confirms DOTS Strep A, Mainline Confirms Strep A, Mainline Confirms III hCG Serum/Urine, hCG Controls, and the urine hCG pregnancy kit product line, and will instead purchase these products exclusively from "OEM suppliers licensed by FDA and adhering to cGMP and who are the holders of valid 510K's." Your response also generally promises to implement and maintain a quality system that complies with FDA requirements by the end of the fourth quarter of 2008, and makes specific promises to undertake certain corrective actions in response to some of the observations explained on the Form FDA 483.
We have reviewed your response and are unable to determine its adequacy at this time because you have not provided evidence of implementation. You state your intention to discontinue manufacturing the above listed devices but have provided no evidence indicating that you have in fact done so, and your promises to comply with cGMP requirements suggest that, to the contrary, you intend to continue manufacturing these products. Your response does not provide any documentation or evidence demonstrating any implementation of any of the corrective actions promised therein.
This letter is not intended to be an all-inclusive list of the violations at your facility. 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 Form FDA 483 issued at the closeout of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems, and in your firm's marketing of devices without marketing clearance or approval. 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.
You should take prompt action to correct these violations. 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/or civil money penalties. 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. 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 (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.
Your response should be sent to Compliance Officer Sandra Williams at the above address. If you have any questions about the content of this letter please contact Ms. Williams at 313-393-8118.
Joann M. Givens