Cardiomed Supplies, Inc. - 564967 - 09/21/2018

WARNING LETTER
SEPT 21, 2018
VIA UNITED PARCEL SERVICE

Mr. Christian G. Dubé
President/Chairman
Cardiomed Supplies, Inc.
199 St David St,
Lindsay, ON K9V 5K7
CANADA

Dear Mr. Dubé:

During an inspection of your firm located in Lindsay, Ontario, Canada on May 28, 2018 through May 31, 2018, an investigatorfrom the United States Food and Drug Administration (FDA) determined that your firm manufactures Phlebotomy Bag with Valve and Dual Floating Dialysis Catheter/Tray. 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 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 Mr. Dubé, President/Chairman dated June 18, 2018 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which 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 adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test that the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a).

For example:

a) Your firm performed validation activities, as documented in the ‘Doboy Hospital Sealer Validation and Inspection Report.’ However, your firm did not establish a procedure to dictate how those activities would be performed, including test methods, process parameters, and acceptance criteria.

b) Your firm utilizes (b)(4) Doboy sealers to seal pouches containing phlebotomy bag devices. The sealing protocol (b)(4); however, the actual sealing parameters, including temperature, seal time, and pressure, where appropriate, have not been established and are not monitored in production. You have at least (b)(4) styles of pouches that may be sealed with the sealers; all of these pouches are sealed at a heat setting of (b)(4).

c) Two "Memo to File" documents covering each of the (b)(4) Doboy sealers, dated June 27, 2016 and January 19, 2017 indicate that favorable results from burst testing of (b)(4) samples was sufficient to validate the equipment at that time. However, you have since begun sterilizing in-house under a different cycle and post-sterilization testing is not being performed. For example,

i)    Since the sterilization was brought in-house, you have not confirmed that Doboy sealer (b)(4) is adequately sealing pouches. Samples sealed on this sealer were originally sterilized prior to testing; and since the sterilization cycles were changed and brought in-house, no further testing of sterile pouches has been performed.

ii)    Samples sealed on the other Doboy sealer, (b)(4), were tested on non-sterile pouches. No testing has been performed on pouches post-sterilization, and, according to the “Doboy Hospital Sealer Validation and Inspection Report,” which reports the results of burst strength measurements for pre- and post-sterilization, the values indicate a decrease in burst strength after sterilization. However, this testing was dated June 27, 2016 and you had not yet brought sterilization in-house. .

d) For the Ethylene Oxide (EtO) sterilization validation completed on or around December 14, 2016 for in-house sterilization processing, the device models evaluated during full cycle runs (b)(4) were not identified in your records. You have not documented that you have established this validation applies to all marketed devices.

e) For your in house Ethylene Oxide (EtO) sterilization validation, residual testing was conducted for three types of devices: phlebotomy bag, SmartTap paracentesis drainage bag and the dual floating dialysis tray. The residual testing was conducted per ISO 10993-7 using the category in the standard for devices with limited exposure (less than 24 hours contact time). However, the dual floating dialysis device is cleared under K042672 for vein insertion up to 12 months (categorized in ISO 10993-7 as permanent exposure greater than 30 days contact).

The residual EtO and ECH acceptable limits vary depending on the type and duration of contact. The daily dose you noted in testing ranges from (b)(4)/device for EtO and (b)(4)/device for ECH. You have failed to establish that you meet residual levels allowable per the standard for permanent contact devices.

We reviewed your firm’s response and conclude that it is not adequate. In the response, you provided two CAPA action plan documents that identify the items listed in FDA Form 483, briefly state corrective actions and a planned completion date. You state that you intend to perform validation or revalidation for your firm’s process to address each item identified in Observation 1 of the 483; however, you have not identified/described how the CAPAs will be implemented. While you have stated you will be validating/revalidating these processes, you have not indicated that you intend to evaluate validation activities associated with the processes for other devices; or described corrective actions to ensure that similar issues do not occur in the future; nor evaluated sources of quality data for existing product to determine whether the lack of adequate validation may have led to distribution of nonconforming product.

2.    Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example:

a) Your "Corrective Action and Preventive Action" procedure (Rev 00 dated 09/05/2017) is inadequate in that:

i)    It does not address how identified quality data sources will be evaluated to identify the need to take corrective or preventive action(s).

ii)    It does not specify that verification/validation activities conducted for effectiveness and analysis of adverse impact on the device will be performed prior to implementation of corrective and preventive actions.

We reviewed your firm’s response and conclude that it is not adequate. In the response, you have provided two CAPA action plan documents that identify the items listed in FDA Form 483, briefly state corrective actions and a planned completion date. You state you intend to update your SOPs related to the observation. However, you have not stated if/how you plan to analyze the sources of quality data to determine whether inadequate procedures resulted in missed quality problems that require corrective action. Additionally, you have not planned to look at previously closed CAPAs to determine whether they were adequately verified/ validated and mitigate gaps, as necessary.

b) CAPA 2017-08 was initiated due to multiple customer complaints related to the safety scalpel included in the dialysis catheter kits. You believe the blade may not be “clicked” into the locked position when received from the supplier. A corrective action was implemented to add a verification of blade retraction at receiving to ensure the blade is locked properly. However, the corrective action did not appear to adequately correct the issue and prevent recurrence, as additional complaints occurred. While there is a 100% visual inspection for the proper placement of the components in the kit tray in your DHR, this step does not verify that the blade is retracted.

In addition, the risk analysis is incomplete for the "Dialysis Catheters Risk Management File" (Rev 00 dated May 31, 2018). The risk analysis does not address risks associated with kit components packaged with the dialysis catheters. You have received multiple complaints for the included scalpel due to it cutting users during opening of the kit and have not adequately identified the actions necessary to prevent recurrence of the problem.

We reviewed your firm’s response and conclude that it is not adequate. You provided a CAPA action plan document that identifies the observation as listed in FDA Form 483, briefly states a corrective action and a planned completion date. You state you intend to update the SOPs related to the observation. Additionally, you intend to consider the risks for the scalpel, ask customers if they need the scalpel to be in the dialysis catheter kits (record survey), and eliminate the scalpel from kits, if needed. However, you have not indicated what actions will be taken to ensure that nonconforming product is not distributed while the investigation is occurring, or whether action is necessary to mitigate risks posed by kits that were previously distributed. Also, you have not indicated that you will evaluate other CAPAs to determine whether the actions taken were effective and ensure that appropriate actions are taken to prevent recurrence. In addition, you have not provided completed SOPs for review, including evidence of implementation and effectiveness.

3.      Failure to establish and maintain design validation procedures to ensure that devices conform to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions, as required by 21 CFR 820.30(g). For example, when the sterilization process was moved in-house and cycle parameters were changed, your firm did not establish whether new testing was required in support of the 5-year expiration date and did not perform testing if needed.

We reviewed your firm’s response and conclude that it is not adequate. In your response, you have provided a CAPA action plan document that identifies the observational items listed in the FDA Form 483, briefly state corrective actions and a planned completion date. You state you will prepare risk assessments of in-house sterilization, sterilization revalidation will be performed, and the sterilization validation protocol will be performed per ISO 11135:2014, and the package validation protocol will be performed and an assessment or justification of the fit/form/function of the device will be prepared as required. However, you have not stated that you plan to evaluate other design validation activities, both for the identified device and others, to determine whether similar issues were manifested.

Given the serious nature of the violations of the Act, devices manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States, known as “detention without physical examination,” until these violations are corrected. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violations described in this letter. We will notify you regarding the adequacy of your firm’s responses and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.

Also, U.S. 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 deviations are reasonably related will not be approved until the violations 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, including 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 (which must address systemic problems) 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. Please provide a translation of documentation not in English to facilitate our review.

Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Inspections Support Branch, White Oak Building 66, Rm 3540, 10903 New Hampshire Ave., Silver Spring, MD 20993.Refer to CMS case # 564967 when replying. If you have any questions about the contents of this letter, please contact: M. Isabel Tejero del Rio, Lead Consumer Safety Officer, Office of Compliance, CDRH at 301-796-5322 or Isabel.Tejero@fda.hhs.gov.

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 yours,
/S/
Ann M. Ferriter
Director, Division of Analysis and Program Operations
Office of Compliance
Center for Devices and Radiological Health

CC:
Jerry Doane
Tobias Systems. LLC
15815 SW 11^th Ct. Road
Ocala, FL 34473
716 7750533
jdoane@usagent-tobias.com

U.S. Food and Drug Administration

Cardiomed Supplies, Inc. MARCS-CMS 564967 — September 21, 2018