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Acrostak Schweiz AG MARCS-CMS 668948 —

Medical Devices

Recipient Name
Mr. Youri G. Popowski
Recipient Title
Acrostak Schweiz AG

Stegackerstrasse 14
8409 Zurich

Issuing Office:
Center for Devices and Radiological Health

United States

Secondary Issuing Offices

United States

CMS # 668948

October 31, 2023

Dear Mr. Youri G. Popowski:

During an inspection of your firm located in Winterthur, Switzerland on June 12, 2023, through June 15, 2023, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the M-Cath Microcatheter and M-Cath Flexy Microcatheter. Both products appear to be intended to provide support to a guide wire while performing percutaneous coronary intervention, facilitate the exchange of guide wires while maintaining access to distal vasculature, and deliver radiopaque contrast media into the coronary vasculature. 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.

Your firm currently holds a 510(k) clearance (K171176) for the M-Cath Microcatheter, which was issued on September 15, 2017. However, the other product marketed by your firm, the MCATH Flexy Microcatheter, was introduced in 2021 without 510(k) clearance as a new design to your firm’s cleared device covered under K171176. The M-CATH Flexy Microcatheter features multiple significant changes or modifications in design, components, method of manufacture, or intended use within the meaning of 21 CFR 807.81(a)(3). Specifically, firm documents inspected by FDA note that the M-Cath Flexy Microcatheter contains different material grades in its proximal, middle, and distal shafts, different colorants, an additional braided shaft outer layer, and a different tip design in comparison to the M-Cath Microcatheter. In addition, the M-Cath Flexy Microcatheter is available in a longer length (150 cm) than the M-Cath Microcatheter.

The changes made to the patient-contacting materials and larger surface area in the M-CATH Flexy Microcatheter can expose the patient to new or different amounts of chemicals compared to the M-Cath Microcatheter, which could result in adverse blood or tissue reactions. In addition, the longer length and different tip design of the M-CATH Flexy Microcatheter can impact the mechanical performance and integrity of the catheter, resulting in vessel damage or embolism. During the management discussion at the end of the inspection your firm noted that you documented the changes made to the M-CATH Flexy Microcatheter internally in a “Letter to File” rather than submitting a 510(k). Your firm to date has also not addressed this issue in any of the responses received by FDA as of the date of this letter.

The changes outlined in this warning letter could significantly affect the safety or effectiveness of the M-CATH Flexy Microcatheter within the meaning of 21 CFR 807.81(a)(3). Accordingly, your firm was required to submit a new premarket notification submission under section 510(k) of the Act, 21 U.S.C. § 360(k), to FDA at least 90 days before you proposed to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of the M-CATH Flexy Microcatheter. See 21 CFR 807.81(a)(3).

You did not submit any new 510(k) in association with the M-CATH Flexy Microcatheter. The M-CATH Flexy Microcatheter is therefore misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not timely notify FDA of its intent to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of the M-CATH Flexy Microcatheter, as required by section 510(k) of the Act.

Our inspection revealed that the M-CATH Flexy Microcatheter is also adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g).

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. 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/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.

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 you dated June 28, 2023 and a second response from Mr. Ghadeer Al Khafagi, Regulatory Affairs Manager, dated September 28, 2023 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 maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met as required by 21 CFR 820.75(b)(2) – Process Validation. More specifically, the environmental control validation activities should be monitored and controlled per the established procedures to ensure that specific requirements continue to be met.

a. For example, both the M-CATH and M-CATH Flexy microcatheters are (b)(4) cleanroom which WI 1007-1: Hygiene Master Plan (Rev. L, approved 31 January 2023) defines as an ISO Class 8 environment per ISO 14644-1. According to the Quality Assurance Manager, your firm has never monitored particle counts in this environment to demonstrate that the environment is adequately controlled (b)(4) are ongoing. The last two Annual clean room qualifications were performed on (b)(4), and (b)(4); (b)(4), your firm has not monitored the clean rooms per the established work instruction and per ISO 14644-1 to establish a Class 8 environment, which requires assessing the environment under normal operating procedures with personnel present and manufacturing operations ongoing. This lack of monitoring during normal operation could underestimate the exposure to contaminants on the device and ultimately for the patient.

The adequacy of your firm’s response dated June 28, 2023, and September 28, 2023, cannot be determined at this time. Although your firm acknowledged that particle count measurements (b)(4), your firm noted that a justification (b)(4). Your firm initiated CAPA: 23CA08 which found that there are no issues from product contamination and determined that no immediate action has been taken, but your firm considers this to be a high priority issue and will take the necessary actions to implement required controls per ISO 14644-1. Although your firm has not found product contamination, your firm has not ensured that the clean room meets the Class 8 environment limits. In the response dated September 28, 2023, your firm stated that the gap assessment has been performed and implemented; however, your firm has not completed planned corrective actions 2-4 which include updating the cleanroom risk assessment file, establishing a procedure for regular airborne particle contamination control, and closing all standard implementation actions. Therefore, the adequacy of this response cannot be determined until the corrective action to establish a procedure for regular airborne particle contamination control has been implemented to assess the clean room per ISO 14644-1 during normal operation with personnel present and verified. To assess the adequacy of your responses to date, your firm should provide the completed clean room validations under normal operating conditions.

b. For example, procedures for documenting process monitoring data have not been adequately established. In the manufacturing work instruction for M-CATH Flexy microcatheter (WI 158-71, Rev. FB; approved 28 September 2022 January 21, 2022) and the work instruction for the M-CATH microcatheter (WI 158-1 Rev. F approved September 28, 2022-09-28), (b)(4). Our investigator confirmed with your firm’s production manager that your firm neither records process parameter settings in the Device History Record nor performs testing to ensure that the (b)(4) is adequately monitored.

The adequacy of your firm’s response dated June 28, 2023, and September 28, 2023, cannot be determined at this time. In the response dated June 28, 2023, your firm noted that (b)(4), which gives assurance that the process is not critical and that (b)(4). Your firm also initiated a CAPA (CAPA:23CA11). In the follow-up response dated September 28, 2023, you noted that your firm has performed a review of the requirements for monitoring and control of processes and updated the related procedures and your firm has created forms for processes with variable parameter settings where no documentation exists. However, to assess the adequacy of your responses to date, your firm should provide the finalized updates to the procedure and/or forms for processes with variable parameter settings (e.g., work instructions, device history record forms, etc.)

2. Failure to establish and maintain design validation procedures to ensure that devices conform to defined user needs and intended uses; to ensure proper risk analysis is completed; and to ensure the results of the design validation, including identification of the design, method(s), the date, and the individual(s) performing the validation are documented in the design history file, as required by 21 CFR 820.30(g).

a. For example, your firm’s risk assessment table (RAR-0005 referenced in FM 21-2, Rev. A, approved 12 July 2022), identifies only one potential harm, inflammatory reaction not requiring medication, for tip separation (risk ID #44) despite the fact that embolism is also listed as a potential risk for tip separation in a note under the causes for risk ID#44. The risk table does not identify nor calculate the risk of embolism resulting from catheter tip separation.

b. For example, your firm’s risk assessment table (RAR-0005 referenced in FM 21-2, Rev. A. approved 12 July 2022) determined that risk ID #44 for tip separation has a probability of occurring remotely (P1) and a negligible severity of S1 for no adverse health consequences. However, per your risk management plan procedure (FM 136-1 Rev B), (b)(4), the probability of this occurrence does not appear to be correct. Furthermore, the severity of an embolism does not appear to be accounted for, as an embolism could result in death. Thus, the current risk assessment table does not appear to address all potential risks associated with tip separation; it underestimates the potential risk probability and severity; and it is unclear if the identified causes and controls adequately address the risks of both inflammatory reaction(s) and embolism with respect to tip separation. As such, the procedures to control the design of the device do not appear to be adequate.

The adequacy of your firm’s response dated June 28, 2023 and September 28, 2023, cannot be determined at this time. In the responses dated June 28, 2023 and September 28, 2023, your firm noted that no planned actions were necessary, CAPA:23CA12 was opened, and a meeting to discuss the risk table shall be held on December 30, 2023 to update the risk table by January 31, 2024. To date, FDA has not yet received updated information regarding the revised risk table reflecting determinations for tip separation risks, mitigations, severity, and occurrences based on the above-noted potential risks associated with tip separation.

c. For example, during the management discussion, the investigator informed your firm that the retrospective design validation study for M-Cath and M-Cath flexy microcatheter is inadequate because its methods do not define the criteria for demonstrating when user needs and intended uses are met. Your firm’s design validation report for M-CATH and M-CATH Flexy microcatheters, REP-00130: Design Validation Report – Microcatheters (Rev. 1, approved 2022-08-19), also does not contain acceptance criteria. As such, it was unclear whether validation demonstrated that user needs and intended uses were met.

The June 28, 2023 and September 28, 2023 responses are not adequate because they do not address this deficiency. During the closeout meeting on 2023-06-15, Mr. Youri Popowski said he understood the discussion item, but no additional response or updated protocols reflecting acceptance criteria were documented in the June 28, 2023 or September 28, 2023 response. Therefore, FDA has not yet received the update protocols to address this observation.

3. Failure to establish and maintain procedures that define the responsibility for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications per 21 CFR 820.90 (b)(2). For example, your firm manufacturing work instruction for M-CATH microcatheters (WI 158-1, Rev. F; approved 28 September 2022) (b)(4).

The adequacy of your firm’s response dated June 28, 2023 and September 28, 2023, cannot be determined at this time. In the response dated June 28, 2023, your firm acknowledged that (b)(4). Your firm noted several planned actions and in the response dated September 28, 2023, your firm noted that your firm has reviewed the procedure related to non-conforming products and corrected them and that your firm has identified existing rework steps and updated traveler records as appropriate. Your firm also noted that these corrective actions are pending for effectiveness checks. To assess the adequacy of your responses to date, your firm should provide an updated copy of these revised procedures and records, including, but not limited to work instructions covering rework and device history record forms containing fields for rework descriptions.

Given the serious nature of the violations of the Act, the M-Cath Flexy Microcatheter manufactured by your firm is subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that this device appears to be adulterated. As a result, FDA is taking steps to refuse entry of this device into the United States, known as “detention without physical examination,” until these violations are addressed. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and address the violation(s) 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.

Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed.

Please note that following the inspection, we reviewed your MDR procedure and would like to bring the following to your attention. Per 21 CFR 803.17(a)(1), a device manufacturer is required to adequately develop, maintain, and implement written MDR procedures. Your firm identified MDR DC03055, MDR Reportability Review Memorandum procedure titled “Medical Device Reporting System US - SOP”, WI 1009-3, Rev. B, dated 2/6/2023 during the inspection. Upon reviewing the procedure, it has been determined that the procedure does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements, as required by 21 CFR 803.17(a)(1). For example, the procedure includes the definitions from 21 CFR 803.3 for the terms “MDR reportable event”, “become aware”, “caused or contributed” and “malfunction”, and the definition for the term ‘reasonably suggests’, found in 803.20(c)(1). However, the procedure omits the definition of the term “serious injury” from 21 CFR Part 803.3. The exclusion of the definition for the term 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). We plan to follow-up on this issue when we review your MDR information submitted to the Agency and at the next inspection

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 address 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. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.

Your firm’s response should be sent by email to CDRHWarningLetterResponses@fda.hhs.gov or by mail to Food and Drug Administration, Center for Devices and Radiological Health, Office of Regulatory Programs, Division of Regulatory Programs 2: Establishment Support, Regulatory Inspections and Audits Team, White Oak Building 66, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #668948when replying. If you have any questions about the contents of this letter, please contact: Samuel Raben, PhD at samuel.raben@fda.hhs.gov or 240-402-6629.

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 any violations and take prompt actions to address any violations and bring the products into compliance.

Sincerely yours,

Bram Zuckerman, M.D.
Office of Cardiovascular Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

Stephen Toupin
7320 NW 12th Street, Suite 103, Miami, FL US 33126

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