Aizu Olympus Co., Ltd.

During an inspection of your firm located in Aizuwakamatsu, Fukushima, Japan, on July 5, 2022, through July 8, 2022, an investigator (or investigators) from the United States Food and Drug Administration (FDA) determined that your firm manufactures sterile and non-sterile Endoscopes and Automated Endoscope Reprocessors. 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 Kenji Matsuoka, President of Aizu Olympus, dated July 29, 2022, 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 and maintain procedures for validating the device design to ensure that devices conform to defined user needs and intended uses and validation shall include testing of production units under actual or simulated use conditions, as required by 21 CFR 820.30(g).

For example: Document (b)(4), “Design Rules” version 13 defines Design Validation as, (b)(4).” However, User-Assessment Procedures for URF-V3/V3R and UFR-P7/P7R Validation Report Document #(b)(4), dated October 4, 2017, states that only the, “(b)(4)” of the URF-V3/V3R and URF-P7/P7R needed to be evaluated. The entire device design was not validated to ensure that devices conform to defined user needs under actual or simulated use conditions. For example, image quality was not validated.

The adequacy of your firm's response cannot be determined at this time. Your firm decided they would re-validate the URF-P7 to cover all user needs. Your firm will determine the due date for the validation activities after your firm completes the design validation plan (due October 14, 2022).

You state that your firm will also revise the design controls procedure to clarify that design validation will cover the entire device under review and determine what elements are required in a justification for the use of an alternate device. Your firm will review design projects for the last two years for similar issues. Your firm plans to complete corrective actions by November 18, 2022. Your firm will train staff on revised procedures. However, the adequacy of the corrective actions cannot be determined at this time because the actions are ongoing. Please provide updates on the corrective actions as they are completed.

2. Failure to 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: the bonding/gluing processes using the (b)(4) and (b)(4) adhesives during final assembly have not been validated. (b)(4) Docking Work Instruction, Document #(b)(4) (among others) follows the application of adhesive with “(b)(4)” which cannot fully verify the application of the adhesive.

Your firm's response is not adequate. Your firm determined the output of ‘preventing screws from loosening’ is not verifiable and you state that your firm will conduct a health hazard evaluation (HHE) by August 31, 2022 to determine the health risk from the screws loosening. Your firm will update their process validation procedures with criteria for when a process is verifiable by October 31, 2022. In addition, your firm will review all manufacturing processes at Aizu Olympus to ensure that processes whose outputs cannot be verified are validated by October 31, 2022. You state that your firm will train staff on revised procedures by October 31, 2022.

Your firm did not state if there are previously distributed devices that were made with specifications that were not validated. Your firm did not provide information on addressing the lack of knowledge of previous curing times and it is unclear how these products meet validation criteria. Your firm’s HHE should address these concerns and determine if a correction or removal is necessary. Your firm should also determine through the HHE whether this issue could have any impact on device reprocessing.

Your firm's response is not adequate because, the sample size for the adhesive process validation is unclear. Secondly, it is also unclear if there are previously distributed devices that were made with specifications that were not validated. Thirdly, how your firm will address the lack of knowledge of previous curing times and determine if products meet validation criteria. Fourthly, it is unclear if inadequate curing of the adhesive could lead to reprocessing issues (e.g. material getting stuck in and around the adhesive and making it difficult to adequately reprocess the device). Finally, your firm should assess if a correction or removal is necessary. Please provide updates on the corrective actions as they are completed.

3. Failure to establish and maintain procedures to ensure that Design History Record (DHR) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured accordance with the DMR and the requirements of 21 CFR 820, as required by 21 CFR 820.184.

For example: the curing time ((b)(4) hours or more) for the adhesive bonding/gluing process during final assembly was not documented on all 11 URF-P7 DHRs reviewed during the inspection. Additionally, the ultrasonic cleaning process used to clean various components during final assembly was not documented on all 11 URF-P7 DHRs reviewed during the inspection.

Your firm’s response indicated that the curing and ultrasonic cleaning process parameters were not documented in the URF-P7 DHR. Your firm’s root cause investigation determined that there was no requirement to record these parameters. Your firm provided:

AMS A001139W1 Device History Record (DHR) Management, rev 14

AMS A00112W1 Preparation of Assembly Work Standards, rev 28

AMS A05209W1 Controls of Process Parameters, rev 36

N-OIS M22003 Cleaning Work Element Standard, Rev 11

Your firm is conducting an HHE of the risk for falling to document the curing time and ultrasonic cleaning parameters. Your firm plans to complete the HHE by August 31, 2022. Your firm also plans to update the DHR for the URF-P7 to include process parameters for the bonding and cleaning processes by August 3, 2022.

Your firm also plans to review AMS A05209W1 Control of Process to determine if there are other process parameters that should be monitored and are not. This review will be completed by September 16, 2022. Your firm will update AMS A05209W1 by December 9, 2022, to:

Specify the curing time be monitored

Include the ultrasonic cleaning parameters

Include any additional missing process parameters.

Your firm will then review all DHRs for currently manufactured devices and remediate gaps as necessary. Your firm will complete the DHR review by January 31, 2022. The adequacy of your firm’s corrective actions cannot be determined at this time because the actions are ongoing. Please provide updates on the corrective actions as they are completed.

Our inspection also revealed that your firm's sterile and non-sterile Endoscopes and and Automated Endoscope Reprocessors 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. These violations include, but are not limited to, the following:

4. Failure to develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17.

For example: during this inspection, your firm acknowledged that it had not established written MDR procedures.

In the response, your firm developed two documents titled “CoE Global MDR: Handling US MDR Reporting for Potential Adverse Event Complaints”, GSOP-8.15-7, Rev. AD, dated 7/13/2022 and “Medical Device Reporting Work Instruction”, OMBS W 8.2.3_01_001, Rev. 13, dated 7/26/2022. The documents collectively were referenced as your firm’s MDR procedure. The document references Aizu Olympus Co. Ltd. as a Manufacturer. Your firm did not provide documentation or evidence of implementation. You state that plans for staff training and MDR reporting process realignment are still ongoing. Therefore, the adequacy of your firm's response cannot be determined at this time. Please provide updates on the corrective actions as they are completed.

U.S. federal agencies may take your compliance history into account when considering the award of 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 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 (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 all 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. Please provide a translation of documentation not in English to facilitate our review. We will notify you regarding the adequacy of your firm's response(s) and the need to re-inspect your firm's facility to verify that the appropriate corrections and/or corrective actions have been made.

Your firm's response should be sent to CDRHWarningLetterResponses@fda.hhs.gov, or if e-mail cannot be used:

Food and Drug Administration - CDRH/ORP/DRP2 CDRH Regulatory Inspections and Audit Team, WO66-1434 10903 New Hampshire Ave. Silver Spring, MD 20993

If you have any questions about the contents of this letter, please contact: Mark Antonino at Mark.Antonino@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.