WARNING LETTER
Q’Apel Medical, Inc.
MARCS-CMS 699244 —
February 05, 2025
Delivery Method:
VIA Electronic Mail
Product:
Medical Devices
Recipient:
Recipient Name
Jodie C. Fam
Recipient Title
Chief Executive Officer
Q’Apel Medical, Inc.
4245 Technology Drive
Fremont
,
CA
94538
United States
Issuing Office:
Center for Devices and Radiological Health
United States
WARNING LETTER
February 5, 2025
Dear Ms. Fam:
During an inspection of your firm located in Fremont, CA on July 29, 2024, through August 8, 2024, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures the 072 Aspiration System (also marketed under the trade name “HIPPO”). 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 any function of the body.
FDA has reviewed information collected during the inspection of your firm located in Fremont, California on July 29, 2024, through August 8, 2024, and determined that the 072 Aspiration System (HIPPO) is 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 (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g), for the device as described and marketed. The device is also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C.
Specifically, FDA cleared, under K222786, the device that you identified in your submission to the agency as the 072 Aspiration System with the following indications, “072 Aspiration Catheter: As part of the 072 Aspiration System, the 072 Aspiration Catheter with a compatible suction pump is indicated for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar, and vertebral arteries) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who failed IV t-PA therapy are candidates for treatment. Aspiration Tubing: As part of the 072 Aspiration System, the Aspiration Tubing is intended to connect the 072 Aspiration Catheter to a compatible suction pump.” The 072 Aspiration System that was presented to us was cleared under K222786 with a design that included a catheter shaft with an inner diameter of 0.072 inch and an outer diameter of 0.0855 inch for the entire catheter working length. The submission that we numbered K222786 did not describe technological characteristics of the distal nitinol tip that would enable expansion of the distal tip to larger diameters or compression of the distal tip during clinical use. However, your firm’s promotion of the device and information collected during the inspection provides evidence that the device as it was designed and developed but not described in your submission includes a nitinol tip with technological characteristics that allow for expansion in diameter and compression in length, i.e., a device for which your firm lacks clearance or approval. Examples of the promotion and information include:
(b)(4)
data report of tip compression testing (“Hippo Tip Vacuum Ball Testing”) was shared via emails exchanged within Q’Apel Medical
(b)(4)
. The data include tip diameter and length measurements of multiple catheter tips (“bad units” and “good units”) while vacuum was applied to a
(b)(4)
ball with a diameter larger than the HIPPO distal tip diameter. Multiple images show increased diameters of the distal region of the nitinol tip expanding around the surface of the
(b)(4)
ball with reported increases in diameters of
(b)(4)
for “good units” and increases in diameter of
(b)(4)
for “bad units.” The
(b)(4)
data reports tip diameters ranging from
(b)(4)
inch with aspiration applied to the
(b)(4)
ball, compared to the relaxed tip diameter of
(b)(4)
inch to
(b)(4)
inch. The
(b)(4)
data reports accompanying changes in tip length of
(b)(4)
(relaxed tip lengths of
(b)(4)
inch, compressed under ball aspiration to lengths of
(b)(4)
inch) for “good units” and
(b)(4)
(relaxed tip lengths of
(b)(4)
inch, compressed under ball aspiration to lengths of
(b)(4)
inch) for “bad units.” The distinction of “good units” and “bad units” is not described in the
(b)(4)
data. However, both “good units” and “bad units” describe evidence of increased HIPPO distal tip diameters and compressed tip lengths when aspiration was applied to the
(b)(4)
balls. The submission K222786 did not provide images or information to show expansion of the distal tantalum markers or compression of tip length of the nitinol tip as shown in the images included in the
(b)(4)
data of tip compression testing (“Hippo Tip Vacuum Ball Testing”).
The “
(b)(4)
” includes a video on page 35 of 45 titled “Mechanism of action,” that shows the nitinol tip of the HIPPO catheter aspirating a simulated clot. The video shows the catheter tip compress near the mid-point of the nitinol tip structure (with possible increased diameter), while the distal tantalum petal markers are obscured by the simulated clot. A second distinct slow-motion video also titled, “Mechanism of action,” is included on page 36 of 45 of the “
(b)(4)
” that shows the nitinol tip of the HIPPO catheter aspirating a simulated clot. This video shows the HIPPO catheter tip prior to contact with the simulated clot and upon contact with the simulated clot, the distal tantalum petal markers on the most distal struts of the nitinol tip are shown to flare at the edges combined with longitudinal compression of the nitinol tip while aspiration is applied to the clot until the clot is fully ingested through the catheter lumen. Page 37 of 45 of the “
(b)(4)
” includes a slow-motion video titled, “Mechanism of action: RED 72,” that shows aspiration of simulated clot with the cleared RED 72 Reperfusion Catheter (K211654) that was cited as a reference device during review of K222786 for the 072 Aspiration System (HIPPO). The video of the RED 72 Reperfusion Catheter does not show compression of the catheter tip or expansion of the distal catheter tip as observed in the videos of the HIPPO device on pages 35 and 36 of 45 of the “
(b)(4)
.” Page 45 of 45 of the “
(b)(4)
” also includes a claim that the HIPPO provides “insightful navigation from a tip that flexes to any clot morphology.” The submission K222786 of the 072 Aspiration System (HIPPO) did not provide images that showed compression of the nitinol tip nor flaring of the distal petals of the nitinol tip as shown in videos presented in the “
(b)(4)
.”
• Drawing CS00788, “072 Catheter Nitinol Tip,” descriptions in the “Design History” notes that revision E updates included, “
(b)(4)
.” The version of the drawing provided in K222786/S001, Appendix 27, was revision D and did not include descriptions of
(b)(4)
specification changes or “
(b)(4)
compression testing with tip compression tool.” The “
(b)(4)
, CS 00788 Catheter Nitinol Tip,” document number QI 01560 describes
(b)(4)
. The images and test methods for compression of the nitinol tip were not described in drawing CS00788, revision D, provided in K222786. The submission K222786 otherwise did not provide images that showed compression of the nitinol tip as described in document QI 01560.
During review of K222786, FDA asked for a description of the principle of operation and mechanism of action of the 072 Aspiration Catheter distal tip, including the tip dimensions related to the dimensions of the remainder of the catheter shaft, in the Refuse-to-Accept (RTA) notification dated September 30, 2022. The response provided in the document “002_Cover Letter_RTA_Final.pdf” of the K222786/S001 submission dated October 24, 2022, stated that the 072 Aspiration Catheter tip had “
the same Internal (0.072”) and External (0.0855”) dimensions (ID, OD) as the rest of the catheter’s usable length. The length of the tip is
(b)(4)
”. The flexible tip is a passive structure that does not have an active mechanism of action and is not self-expanding
.” The information gathered in the inspection conducted July 29, 2024, through August 8, 2024, at your firm raises concerns that the information provided to FDA for review in K222786 did not accurately disclose the technological characteristics of the nitinol tip and the changes in diameter and length of the distal tip that could be exhibited during use conditions for aspiration of thrombus from patients experiencing acute ischemic stroke. These different technological characteristics of the nitinol tip to change in length and diameter constitute a change or modification in the device that could significantly affect the safety or effectiveness of the device (e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process) (21 CFR 807.81(a)(3)).
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 FDA. See 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.
Our office requests that Q’Apel Medical cease any activities that result in the misbranding or adulteration of the 072 Aspiration System (HIPPO), such as the commercial distribution of the device for the uses discussed above.
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 response from Jim Talbot, Vice President Regulatory, Quality, and Clinical Affairs dated August 28, 2024, September 26, 2024, and November 27, 2024, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that 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 document design input requirements as required by 21 CFR 820.30(c).
For example, your firm did not adequately define the physical, performance, and other design requirements for design inputs to include tip compression, aspiration/suction pump, tip deflection, and treatment location for your firm’s 072 Aspiration System (Hippo), which are identified in your documents titled, Product Specification 072 Aspiration System (PS 00922, Rev. G) and Customer Requirement Specification Form (CRS 00848, Rev. D).
We reviewed your firm’s response and conclude that it is not adequate. Your firm has not adequately defined specifications for tip elongation and compression (PS-11.5.2), aspiration flow rate (PS-11.5.3) and tip deflection (PS-11.5.9) that are identified in your document titled, Product Specification, PS 00922, Revision H.
Your firm provided the document titled, Draft Research Report, Aspiration System, Aspiration Flowrate Acceptance Criteria, RR 02139, in your response dated August 28, 2024. This document appears to leverage previous testing of the Aspiration flowrate to define measurable acceptance criteria for future Aspiration Flowrate testing. The comparative device testing was conducted on a sample size of three
(b)(4)
. The conclusion states an acceptance interval for the average flow rate is
(b)(4)
. This value was not reflected in your Product Specification documentation or the Test Protocol, TP 00927, which is to be executed for future verification testing by a third-party service provider. It is not clear what this data will be used for.
Please evaluate the adequacy of your corrective actions related to design inputs and continue to provide us information related to your ongoing corrective actions.
2. Failure to adequately establish and maintain procedures for design verification as required by 21 CFR 820.30(f).
For example, your firm did not adequately define acceptance criteria that can be verified for Aspiration Flowrate, Tip Deflection, and Tip Compression and Elongation in your protocol titled, Test Protocol, Device Performance Design Verification Validation, FG 00806, FG 00995 (TP 00927, Rev. C).
Additionally, the verification test performed for Aspiration Flowrate and documented in Test Report 072 Aspiration System, Design Verification Validation, FG00806, FG 00995, Aspiration Flowrate (TR 00927-15, Rev. A), was conducted using
(b)(4)
vacuum setting, whereas the Instructions for Use for the device describes
(b)(4)
vacuum settings the device can be used with. There is no documented rationale to justify why testing flowrate at
(b)(4)
setting is adequate.
We reviewed your firm’s response and conclude that it is not adequate. Your firm still has not implemented your design control procedure, in that your design verification protocol continues to not establish acceptance criteria for specifications to include tip deflection, elongation and compression, and aspiration flow rate that can be verified. Additionally, your firm’s rationale for testing a
(b)(4)
vacuum pressure is inadequate. Verification testing should be performed for all
(b)(4)
ranges utilized by the device.
Your firm stated that you are
(b)(4)
. However, the Test Report has not been provided to FDA.
Please evaluate the adequacy of your corrective actions related to design verification and continue to provide us information related to your ongoing corrective actions.
3. Failure to adequately establish and maintain procedures for design change as required by 21 CFR 820.30(i).
For example, your firm has not implemented your procedure for design changes titled, Design Control (SOP 00003, Rev. C, effective date 02/01/2021 & Rev. D, effective date 11/14/2022) (revisions in effect when design changes were processed), which states that design changes are subject to original verification or validation tests and if no test(s) or a subset is planned, a justification is required. Specifically, your firm has not evaluated the impact changes may have to original verification or validation tests or provided a justification if no test(s) or a subset is required. Design changes were made to update the specification for your 072 Cather, Nitinol Tip
(b)(4)
(under ECO 1142) and to update the
(b)(4)
specification (under ECO 1360)
(b)(4)
acceptability range
(b)(4)
. No assessment was documented of the potential impact the changes could have on completed verification and/or validation tests.
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s reevaluation of ECO 1360 states that the firm’s risk management document, RM 00951, Design FMEA, 072 Aspiration System, was updated in ECO 1300 to capture the new risk identified with SA 00570
(b)(4)
. It further states that testing was performed via
(b)(4)
. Your firm determined that verification and/or validation testing was not required. This assessment is inadequate. Testing should be documented and performed according to a defined protocol.
Please evaluate the adequacy of your corrective actions related to design changes and continue to provide us information related to your ongoing corrective actions.
4. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit as required by 21 CFR 820.198(a).
For example, your firm has not adequately implemented your complaint procedure, Complaint Handling and Customer Feedback (SOP 00148, Rev. M, effective date 02/27/2024), which requires returned product analysis to be completed within 30 days after receiving the product from the field. Specifically,
CN 0251 was opened to document a complaint reporting resistance was felt while the Hippo 072 Aspiration Catheter was inside an access catheter. The associated complaint product was received by your firm on 06/12/2024 under RMA0494 and logged in RMA log. As of 08/02/2024 the complaint product has not been investigated.
CN 0252 was opened to document a complaint reporting stretching on the distal portion of the 072 Aspiration Tubing. The associated complaint product was received by your firm on 06/27/2024 under RMA0493 and logged in RMA log. As of 08/02/2024 the complaint product has not been investigated.
We reviewed your firm’s response and conclude that it is not adequate. Removing the 30-day timeframe for completing the returned product analysis may impact your firm’s assessment of complaints that are determined to be malfunctions and thus your firm’s adherence to reporting timeframes required as part of the Medical Device Reporting (MDR) Regulation (see 21 CFR Part 803). Your firm should provide a risk-based justification for the removal of the requirement and evaluate complaints to determine if any unreported MDRs were found.
5. Failure to adequately establish and maintain procedures for document control as required by 21 CFR 820.40.
For example, your firm did not adequately implement your document control procedures as outlined in
(b)(4)
(SOP 00002, Rev. R, effective date 05/24/2024 (current revision), Rev. P, effective date 02/02/2024, and Rev. N, effective date 07/14/2023. Section 6.1 of your procedure titled
(b)(4)
(SOP 00460, Rev, A, effective date 9/14/2020)
(b)(4)
. Specifically, the following promotional material for the 072 Aspiration System (Hippo) was not developed and approved per the firm’s document control procedures:
A video clip depicting the tip of the Hippo aspiration catheter flaring out
A video clip referring the to the Hippo aspiration catheter tip as adaptive, depicting the tip of the Hippo aspiration catheter flaring out, and referencing R&D Aspiration Grip Force data
A press release announcing the clearance of the Hippo 072 Aspiration System that describes the aspiration tip as adaptive
We reviewed your firm’s response and cannot determine the adequacy at this time. Your firm extended the target completion date to 11/25/2025, for compiling of a list of marketing/ promotional content for their Armadillo and Walrus devices and evaluating if product claims were found.
(b)(4)
; therefore, we request that you continue to provide information related to the
(b)(4)
.
Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter 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.
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. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.
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, 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 (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. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. 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 via e-mail to: Jessica Mu, Assistant Director at CDRHWarningLetterResponses@fda.hhs.gov. Refer to the Unique Identification Number,
CMS # 699244
, when replying. If you have any questions about the contents of this letter, please contact: Shaquenta Perkins at shaquenta.perkins@fda.hhs.gov or 619-941-3763.
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,
/S/
RDML Sean M. Boyd, MPH, USPHS
Director
Office of Regulatory Programs
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
Content current as of:
03/11/2025
Regulated Product(s)
Medical Devices