Inspections, Compliance, Enforcement, and Criminal Investigations
Transonic Systems Inc 6/19/13
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
New York District
Food & Drug Administration
158-15 Liberty Avenue
Jamaica, NY 11433
June 19, 2013
WARNING LETTER NYK-2013-21
VIA UNITED PARCEL SERVICE
Mr. Cornelis J. Drost, President & CEO
Transonic Systems, Inc.
34 Dutch Mill Road
Warren Road Business Park
Ithaca, NY 14850
Dear Mr. Drost:
During an inspection of your firm located in Ithaca, NY, on February 25, 2013, through March 21, 2013, an Investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures and distributes, in part, the COstatus system that is used in conjunction with an Arteriovenous (AV) Loop Kit and other related accessories. These medical devices are utilized for the measurement of cardiac output and related hemodynamic and blood volume parameters. 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 is intended to affect the structure or function of the body.
Quality System Violations
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, its 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 your firm’s response dated April 8, 2013, concerning our Investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to you at the close of the inspection. We address this response below, in relation to each of the violations. These violations include, but are not limited to, the following:
- The design history file does not demonstrate that the design was developed following the requirements of 21 CFR 820, as required by 21 CFR 820.30(j). Specifically, your procedures for design controls require the use of a phase and gate approval system. Gate 4 approval ends the design phase of the project and certifies the product has been designed under the firm's quality system; the product is ready to be manufactured and marketed; ready for release to production and transfers the design. The following are instances of inadequate design controls pursuant to established procedures and incomplete design history files.
- Gate 4 for the COstatus system monitor was granted final approval on 1/29/10. A total of (b)(4) COstatus flowmeters (HMC101) have been manufactured dating from July 2008 to May 2012. COstatus units were either manufactured or released to customers prior to Gate 4 approval. Systems include but not limited to (b)(4) (s/n: (b)(4)), (b)(4) (s/n: (b)(4)), (b)(4) (s/n: (b)(4)), (b)(4) (s/n: (b)(4)) and (b)(4) (s/n: (b)(4)).
- The design history file for the COstatus monitor (HCM101) is incomplete in that it lacks documentation of what was reviewed during established design reviews (i.e. Gates) as follows: for Gate 2, forms SRS HCP101 Rev. 1 & VPH2J Rev. 1 were not included in the DHF; for Gate 3, no documentation of the case studies reviewed were included in the DHF; and for Gate 4, no form QAF384 was included in the DHF.
- The AV Loops (ADT2005D = HCS3011) design history file was incomplete in that no detailed report and results were maintained for the pressure leak test data as stipulated in the verification report for the disposable AV loop (VRADT2005 Rev. 1).
- AV loops (ADT2005E= HCS3021) have been manufactured and released for customer use without Gate 4 review and approval. One customer includes (b)(4) (lots 101310, 10912, 022912, & 102412).
The adequacy of your response to this observation cannot be adequately assessed until all referenced procedures, work instructions, forms and tasks are updated/complete and can be reviewed by FDA.
- Design validation did not ensure the device conforms to defined user needs and intended uses, as required by 21 CFR 820.30(g). Specifically, design verification and validation activities for the COstatus system were executed under the VR COstatus Rev. 2 COstatus Acquisition Software Verification Report, dated 1/29/10; VRHCM101-002 Rev. 1 Verification Report for the HCM101 Monitor, dated 1/3/08; and the COstatus Beta-site Feedback Summary; COstatus Acquisition Software Validation Report, dated 3/31/10. These activities have failed to demonstrate that the COstatus system conforms to defined user needs and intended uses. For example, intended use of providing clinically relevant data to healthcare providers treating critically ill patients; the platform must be able to be moved easily from patient to patient.
Your response to this violation is inadequate as there is no commitment to perform an appropriate design validation.
- Results of the validation of the device software were not adequately documented, as required by 21 CFR 820.30(g). Specifically, the COstatus Acquisition Software Validation Report, Rev. 1, was approved on 3/31/10. This validation was executed using three HCM101 monitors (s/n: A81019, A81020& A81096). The validation results for the three monitors were not maintained. The report documents results of one system without a documented conclusion.
The adequacy of your response to this observation cannot be determined at this time. In your response to this violation you state that a work instruction (ENG 11.0, Validation and Verification Template Instructions) and form (QAF523, Verification, Validation, and Baseline Test) were created in response to this observation. However, you did not provide these documents in your response for review.
- Acceptance criteria were not established prior to the performance of validation activities, as required by 21 CFR 820.30(g). Specifically, COstatus system verification and validation activities were executed under the VR COstatus Rev. 2 COstatus Acquisition Software Verification Report, dated 1/29/10; VRHCM101-002 Rev. 1 Verification Report for the HCM101 Monitor, dated 1/3/08; COstatus Beta-site Feedback Summary; and the COstatus Acquisition Software Validation Report, dated 3/31/10. Acceptance criteria were not established prior to executing these activities.
Your response to this violation is inadequate because you fail to address why acceptance criteria was not established and documented prior to the execution of validation activities. Also, your response fails to demonstrate how you plan to correct this violation moving forward. Your validation reports should have had a documented conclusion of whether or not established acceptance criteria were achieved.
- Corrective and preventive action activities and/or results have not been adequately documented, as required by 21 CFR 820.100(b). Specifically, corrective and preventive action activities are inadequate as follows:
- CAPA 0029 was initiated in response to customer feedback concerning leakage being noticed with HCS3011 AV Loops during use. You have failed to capture all lots affected by the identified problem (e.g. Lot #102810). The CAPA failed to address and document all failure modes associated with leaking AV Loops (e.g. blood leaked into cassette, the venous part of tube was leaking, a leak in the AV loop, the AV loop on arterial side failed). This CAPA was closed on 3/13/12 and corrective actions did not demonstrate that the actions were fully effective. For example, complaint 5073, that disclosed broken tubing, was received on 8/14/12.
- CAPA 0042 was initiated in response to customer feedback concerning COstatus monitors bringing up a message stating "Turn Off then Turn On" and noting that the monitor does not proceed further even after restarting. You have failed to document the investigation activities that led to the corrective actions.
The adequacy of your response to this observation cannot be adequately assessed until SOP 8.5.2/3 (CAPA) & work instruction QA 188.8.131.52 (Failure Investigation) are complete and can be reviewed by FDA. Furthermore, you did not indicate if a retrospective review of the CAPA’s described in the observation would be performed.
- Complaints involving the possible failure of a device, labeling, and packaging to meet any of its specifications were not reviewed, evaluated, and investigated where necessary, as required by 21 CFR 820.198(c). Specifically, all complaints are processed through the Customer Service Department. In turn a CRS determines whether the reported event is a complaint that is a device related issue or service related issue. The following represent examples of COstatus related complaints where the events were determined to be service related and were not reviewed, evaluated, and investigated as a complaint in accordance with established procedures. Customer service tickets include: 5025, 4176, 4212, 2354, 2670, 4352, 2714, 1374, 1789, 5881, and 1136. Additionally, other than warranty dates, servicing dates were not documented.
The adequacy of your response to this observation cannot be adequately assessed until work instruction QA 184.108.40.206 (Customer Feedback and Adverse Event Reporting) is complete and can be reviewed by FDA. Also, we must await the outcome of your QA review of non-warranty and service issues for trending and complaint analysis in conjunction with repair department personnel.
- Records of complaint investigations do not include required information, as required by 21 CFR 820.198(e). Specifically, customer service tickets of complaints involving COstatus AV Loop leak issues were received between 4/20/11 and 2/13/12. Customer service tickets included: 2898, 3045, 3157, 3346, 3352, 3634, 3778, 4007, & 5073. The complaint records lacked complete documentation of investigation activities including the results and dates of the investigation. In addition, complaint records do not document whether or not corrective action is required.
The adequacy of your response to this observation cannot be adequately assessed until work instruction QA 220.127.116.11 (Failure Investigation) is complete and can be reviewed by FDA.
- Process control procedures that describe any process controls necessary to ensure conformance to specifications have not been adequately established, as required by 21 CFR 820.70(a). Specifically, AV Loops have been manufactured under Engineering Project Requests and you have not established procedures for handling these requests. It is unclear as to whether products manufactured under EPRs need to conform to specifications and can be released for distribution. In addition, forms utilized for EPRs lack traceability for which components and accessories are manufactured under EPRs.
The adequacy of your response to this observation cannot be adequately assessed until a subsequent FDA inspection confirms implementation.
Our inspection also revealed that your devices are misbranded under 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 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 (MDR) Regulation. 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. After reviewing your firm’s procedure titled, “Customer Feedback & Adverse Event Reporting P14.1 Rev. G effective 5/18/11”. The following issues were noted:
(1) QA 4.0 Rev. F 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 does not include definitions for the terms "remedial action” found in 21 CFR 803.3 and "reasonably known" and "reasonably suggests" found respectively in 21 CFR 803.50(b) and 803.20(c)(1). The exclusion of 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).
(2) QA 4.0 Rev. F does not establish internal systems that provide for a standardized review process or procedure for determining when an event meets the criteria for reporting under this part. Specifically, the following was not addressed:
a. The procedure, as written does not specify who makes the decision for reporting events to FDA.
(3) QA 4.0 Rev. F 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 initial, supplemental or follow-up report and the requirements for such reports.
(4) QA 4.0 Rev. F does not describe how your firm will address documentation and record-keeping requirements, including:
a. Documentation of adverse event related information maintained as MDR event files.
b. Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
In addition, QA 4.0 Rev. F, “Medical Device Reporting and Vigilance Reporting,” includes references to baseline reporting and annual certification, which are no longer required. We recommend that all references to Baseline Reports and Annual Certification be removed from your firm’s MDR procedure (see: 73 Federal Register Notice 53686, dated September 17, 2008; and Fourth Notice, Federal Register, dated March 20, 1997: Medical Device Reporting, Annual Certification, Final Rule, respectively).
We reviewed your firm’s response and conclude that the adequacy of the response cannot be determined at this time. Your firm plans to revise its current MDR procedures by May 31, 2013. However, without this documentation in hand, we cannot make an assessment with respect to adequacy.
If your firm, wishes to submit MDR reports via electronic submission it can follow the directions stated at the following URL:
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 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 written response should be sent the Food and Drug Administration; Attention:
LCDR Frank Verni
U. S. Food and Drug Administration
158-15 Liberty Avenue, Room 4050
Jamaica, NY 11433
If you have any questions about the content of this letter please contact: LCDR Verni at (718) 662-5702.
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 ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Form FDA 483, Inspectional Observations (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management 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.
Ronald M. Pace
New York District