Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|Los Angeles District|
Irvine, CA 92612-2506
VIA UNITED PARCEL SERVICE
October 7, 2014
Ms. Shigeko Tanaka
Alpha Medical Instruments, LLC.
23455 Madero, Suite B
Mission Viejo, CA 92691
Dear Ms. Tanaka:
During an inspection of your firm located in Mission Viejo, California, on August 5, 2014, through August 14, 2014, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures angiographic balloon catheters. 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 from you, dated September 2, 2014, 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 establish procedures for corrective and preventive action, as required by 21 CFR 820.100(a). For example:
a) CAPA 104 was opened on January 10, 2013, concerning non-conformities regarding balloon extension air leaks. The CAPA report references multiple root causes for these leaks; however not all of these potential causes were analyzed and investigated. Your records reference that personnel were retrained, but the corrective actions for which they were retrained were not documented. Additionally, this CAPA was closed on February 22, 2013 without documentation that an effectiveness check was performed. The following were observed to have taken place after this CAPA was closed:
- Non-Conforming Report #58 dated 10/09/2013 references (b)(4) Wedge Balloon Catheter assemblies, (b)(4), having air leaks (22% of this lot had this defect). These non-conformities were not analyzed, and you did not identify the action(s) needed to correct and prevent their recurrence.
- Non-Conforming Report #59 dated 10/10/2013 references (b)(4) balloon extensions of the Angiographic Balloon Catheter assemblies, (b)(4), having air leaks (100% of this lot had this defect). These non-conformities were not analyzed, and you did not identify the action(s) needed to correct and prevent their recurrence.
- Complaint YR-14-8, dated 06/02/2014 referenced a balloon extension leak. The complaint file stated that no CAPA would be taken.
- Complaint YR-14-10, dated 06/09/2014 referenced a balloon extension leak. CAPA 110 was opened on 06/09/14 and closed on 06/10/14. The CAPA resulted in updated Instructions for Use to test balloon integrity before use, and implementation of a new SPO, GMP 300-900-004, Catheter Inspection with a Guide Wire, Phase II. No effectiveness check was performed or required in this CAPA.
b) With respect to non-conformities referencing needle protective sheaths falling off inducer needles of the DPX kit, CAPA 107 was opened on March 18, 2013. The root cause was identified, referencing that the manufacturer of the needle provided a slightly smaller needle sheath of a softer material, causing the protective sheath to come off the needle hub flange. The manufacturer was contacted regarding this discrepancy, and there was no documentation that an effectiveness check was performed for the corrective action.
Complaint YR-13-8 was reported on 11/20/2013, which was after this CAPA was closed. This complaint referenced protective sheaths falling off (b)(4) needles (6%) in the DPX Kit, (b)(4). The complaint was attributed to the assembler, and did not reference CAPA 107.
We reviewed your firm’s response, dated September 2, 2014 and conclude it is not adequate. Your promised corrective actions include reviewing of NCRs and complaints, CAPAs and verifying or validating corrective actions, and to review and make changes in your CAPA procedure, and to train employees. Your firm has not submitted documentation that includes evidence of the implementation of these corrective actions.
2. Failure to establish procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).
For example the following complaint files were incomplete:
- Complaint Number YR-14-11 references a “big lumen clog.”
- Complaint Number YR-14-10 references that the balloon would not inflate, the balloon would not deflate, and there was guide wire passage problem.
- Complaint Number YR-14-8 references that the balloon would not inflate and there was guide wire passage problem.
Each of these complaints were referenced as not being an MDR reportable event, yet the complaint file and investigation for each complaint did not reference whether the subject device was being used for treatment. Additionally, these complaint files did not reference whether your firm replied to the complainant.
We reviewed your firm’s response, dated September 2, 2014 and conclude it is not adequate. Your promised corrective actions include reviewing complaints received during the past year, and to review these for MDR reportability, and to determine if your complaint handling procedure needs to be revised. Your firm has not submitted documentation that includes evidence of the implementation of these corrective actions.
3. A process whose results cannot be fully verified by subsequent inspection and test has not been validated according to established procedures, as required by 21 CFR 820.75(a). For example, process validation for cement bonding and tensile strength has not been performed for the manufacturing of your balloon extension assemblies, which are components of your wedge pressure catheters.
We reviewed your firm’s response, dated September 2, 2014 and conclude it is not adequate. Your promised corrective actions include doing a thorough evaluation of all production processes to determine if they need to be validated and if the parameters need to be controlled, and to validate these processes, as well as all future new processes. Your response did not include evidence your corrective actions have been implemented.
4. Production processes were not developed, conducted, and monitored to ensure that a device conforms to its specifications, as required by 21 CFR 820.70(a). For example, the apparatus used to perform Flow Leak Test and Air Check Test on in-process catheter assemblies has not been qualified for use to ensure that it is suitable for its intended purpose and capable of producing valid results. Additionally, this
apparatus is not calibrated or part of a calibration schedule.
We reviewed your firm’s response, dated September 2, 2014 and conclude it is not adequate. Your stated corrective actions include qualifying the apparatus to perform this test. No evidence of implemented corrective actions was included.
5. The device history record does not demonstrate that the device was manufactured in accordance with the device master record, as required by 21 CFR 820.184. For example:
- The Wedge Pressure Balloon Assembly Traveler, Drawing Part # (b)(4), identifies that Flow Leak Tests are to be performed per GMP 300-900-001 release date 4/15/2009. GMP 300-900-001 indicates the pressure as (b)(4) psi. Catheter Testing Records for Lot (b)(4) references are test pressures were performed at (b)(4) psi. Your firm has not verified that the change to the test procedure does not affect flow test results.
- Operation 80 on the Balloon Extension Assembly Traveler references "Perform Pull Strength - Tensile Test" for two samples; however according to your firm’s management, tensile tests are not performed on every lot produced.
We reviewed your firm’s response, dated September 2, 2014 and conclude it is not adequate. Your stated corrective actions include confirming the correct pressure to conduct the Flow Leak Test, and to perform pull strength testing on every lot produced on the Balloon Extension assemblies, and to evaluate test processes to determine whether they need to be validated. No evidence of implemented corrective actions was included.
6. Requirements that must be met by suppliers have not been adequately established, as required by 21 CFR 820.50(a). For example, you purchase inducer needles and sheaths from (b)(4). This supplier is listed on your Approved Supplier List, 2014, and per this list requires an on-site audit, and a quality questionnaire to be filled out for this supplier. You did not maintain records that this supplier met the requirements of your Supplier/Vendor Evaluation Procedure, QSOP-1006, Rev. F.
We reviewed your firm’s response, dated September 2, 2014 and conclude it is not adequate. You did not supply a quality questionnaire for this supplier, and your promised corrective actions include reviewing supplier files to ensure they are complete, and to have the suppliers fill out FORM 1018, your supplier inspection/questionnaire, and to ensure this form is filled out for future suppliers. No evidence of implemented corrective actions was included.
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 firm’s response should be sent to: Tamara Umscheid, Acting Director, Compliance Branch, Food and Drug Administration, 19701 Fairchild, Irvine, CA 92612-2506. If you have any questions about the content of this letter please contact: Dr. William Vitale at 949-608-2919.
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.
Alonza E. Cruse, Director
Los Angeles District
Harlan Loui, Acting Chief
California Department of Public Health
Food and Drug Branch
1500 Capitol Avenue, MS-7602
Sacramento, California 95899-7413