Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Los Angeles District
Irvine, CA 92612-2506
VIA UNITED PARCEL SERVICE
May 21, 2015
Mr. Brad Sharp, C.E.O.
Insightra Medical, Inc.
9200 Irvine Center Drive, Suite 200
Irvine, CA, 92618-2794
Dear Mr. Sharp:
During an inspection of your firm located in Irvine, California from February 19 – 24, 2015, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Intra-Aortic Balloon Catheters and Inguinal Hernia Implants. 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.
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 letter from Neerav Parikh, QA/RA Specialist dated March 12, 2015 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, 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 establish procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR Part 820.198(a).
Specifically, Product Complaint Handling and Post Market Surveillance Procedure, RA2-0007 Rev 15:
a) Section 7.1.5 Complaint Evaluation and Investigation states “QA shall coordinate the review and evaluation of all complaints to determine the level of investigation that is necessary." The procedure does not delineate the different levels of investigation nor does it describe the investigation procedures.
b) Section 7.1.5, states "Investigations shall be performed in such a way that all regulatory requirements are met." A review of 12 complaints revealed that 4 were not adequately evaluated and investigated to determine the root cause of the device failure as exampled by complaint numbers (b)(4)
- (b)(4) - Product Complaint Report, Summary of Investigation states “Patient information not available; therefore, correct catheter sizing cannot be confirmed”. However, the product complaint form received by your firm does in fact contain the patient information of age, gender, weight, height, and body mass index. In addition, post complaint correspondence indicates that two (2) videos were provided by (b)(4), who reported the complaint; there is no discussion in the investigation summary that the videos were reviewed as part of the investigation.
- (b)(4) - This complaint involved a patient death. The summary of the complaint investigation listed in Section 7 of the Product Complaint Report states “An investigation of the incident was conducted with distributor (b)(4); however, the IAB catheter was not available for evaluation and no further conclusions could be made.”
- (b)(4) - The summary of the complaint investigation listed in Section 7 of the Product Complaint Report states “Very limited information provided on patient and event. An investigation of the incident was conducted with distributor (b)(4); however, the IAB catheter was not made available for investigation and no further conclusions could be made.”
- (b)(4) - The summary of the complaint investigation listed in Section 7 of the Product Complaint Report states “Product not returned and an investigation complaint could not be performed. All Insightra IAB are 100% cycle tested during manufacture.”
In instances when your distributor does not provide the information necessary to complete an investigation you should attempt to contact the end user (i.e. the complainant) directly; the end user contact information was included on complaint reports (b)(4) and there are no documented attempts to contact them directly. In addition, when the product subject to a complaint is not available or not returned, FDA recommends that your investigation includes additional steps such as: testing any reserve samples or products manufactured around the time of the manufacture of the subject device; reviewing the Device History Records for the device; analyzing any related service records; and analyzing any CAPA and non-conforming data that is related to the subject device. There is no evidence in your complaint investigation reports (b)(4) that any of those actions were taken.
c) Section 7.4 Complaint File Closure requires "QA will close the file within 30 working days". The procedure does not provide for allowances when additional time is needed to complete an investigation.
The adequacy of your firm’s response cannot be determined at this time as your corrections are reportedly in-progress. Your response states your complaint handling procedure will be revised to include the following: a categorization of complaint types and minimum investigation criteria for each type of complaint; include end user contact and number of contact attempts requirement; include complaint log with complaint file to record and summarize complaint activity history; and update to clarify that 30 day closure is an internal goal for timely complaint closure and resolution; additional days are permissible if required to complete the investigation. Your estimated completion date is 06/30/2015.
Our inspection also revealed that your firm’s 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 device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant violations include, but are not limited to, the following:
Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17.
For example, after reviewing your firm’s MDR procedure, collected during the inspection and titled “RA2-0007 Product Complaint Handling and Post Market Surveillance”, Rev. 15, dated May 13, 2014, the following issues were noted:
1. 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. For example:
a. The procedure omits definitions of the terms “become aware,” and “caused or contributed,” found in 21 CFR 803.3 and the definition for the term “reasonably suggests,” found in 803.20(c)(1). The exclusion of the definitions for 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. The procedure does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
a. The procedure does not contain or refer to instructions for how to complete the FDA 3500A form.
b. The circumstances under which your firm must submit supplemental or follow-up and 5 day reports and the requirements for such reports.
c. The procedure does not include the address for where to submit MDR reports: FDA, CDRH, Medical Device Reporting, P. O. Box 3002, Rockville, MD 20847-3002.
3. The procedure 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. Information that was evaluated to determine if an event was reportable.
c. Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable.
d. Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
Your firm’s procedure includes references to baseline reports. Baseline reports are no longer required and we recommend that all references to a Baseline Report be removed from your firm’s MDR procedure (see: 73 Federal Register Notice 53686, dated September 17, 2008).
The eMDR Final Rule requiring manufacturers and importers to submit electronic Medical Device Reports (eMDRs) to FDA was published on February 13, 2014. The requirements of this final rule will take effect on August 14, 2015. If your firm is not currently submitting reports electronically, we encourage you to visit the following web link for additional information about the electronic reporting requirements:
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.
Please refer to WL #20-15 when replying and send your reply to the Food and Drug Administration, Attention:
CAPT Dan Cline, Acting Director
Los Angeles District
Irvine, CA, 92612-2506
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.
If you have questions regarding any issues in this letter, please contact David Whitman, Compliance Officer at (619)-941-3769.
Alonza E. Cruse, Director
Los Angeles District
David M. Mazzera, Ph.D.
Chief, Food and Drug Branch
California Department of Public Health
1500 Capitol Avenue, MS-7602
Sacramento, California 95899-7413