- Delivery Method:
- United Parcel Service
- Medical Devices
Recipient NameMs. Kim S. Abrano
- Lymol Medical Corporation
4 Plympton Street Woburn, MA
Woburn, MA 01801
- Issuing Office:
- Office of Medical Device and Radiological Health Operations (Division 1 East)
CMS # 606833
April 7, 2020
Dear Ms. Abrano:
The United States Food and Drug Administration (FDA) conducted an inspection of your firm’s medical device operations at Lymol Medical Corporation, 4 Plympton Street, Woburn, MA 01801, from February 3, 2020 through February 12, 2020. During the inspection, an FDA investigator determined that your firm is a manufacturer of Elite X Class Rigid Bronchoscope System and Premier S Class Silicone Stents. 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. These violations include, but are not limited to, the following:
1) A process whose results cannot be fully verified by subsequent inspection and tests has not been validated according to established procedures, as required by 21 CFR 820.75(a). Specifically, your firm failed to validate the manual cleaning processes, sterilization processes, and storage conditions for your LYMOL Medical Elite X Class Rigid Bronchoscope System and LYMOL Medical Optical Telescopes. For example:
A) Your firm’s “Reusable Rigid Bronchoscope system – Instructions for Cleaning and Sterilization Rev 3 -07/19” procedure for LYMOL Medical Elite X Class Rigid Bronchoscope System provides instructions to the hospital for manual cleaning of all components for the rigid bronchoscope system by immersing components into a cleaning/disinfecting solution, then rinsing with distilled or de-mineralized water and drying the device before sterilizing the device.
B) Your firm’s recommended sterilization of the Rigid Bronchoscope involves an autoclave or vacuum process (Prevac-Cycle) at a temperature of 270 degrees Fahrenheit to 275 degrees Fahrenheit, and gas sterilization involving 6% Ethylene Oxide and 94% Carbon Dioxide.
C) Your storage temperature for the Rigid Bronchoscopes is from 50 degrees Fahrenheit to 122 degrees Fahrenheit and your firm recommends storing the devices properly to avoid damage.
D) Your firm’s procedure for cleaning Optical Telescopes involves manual cleaning by immersing the telescopes in a disinfecting/cleaning solution (the maximum time for telescopes to be in the cleaning solutions is 30 minutes since long term exposure to cleaning solutions and detergents may damage the telescope) and rinsing with de-mineralized water and drying with a soft cloth or compressed air.
E) Your storage temperature for the optical telescopes is from 50 degrees Fahrenheit to 122 degrees Fahrenheit, and your firm recommends storing the instruments properly to avoid any damage.
None of these activities described above were validated by your firm.
2) Failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implantation, as required by 21 CFR 820.30(i). Specifically, procedure “QMS-026, Design and Development, version 1” states under section 1 that (b)(4). Your firm made a design change ((b)(4)) during production after receiving a request from a customer to (b)(4) so that the telescope does not get stuck in the bronchoscope. The design change to the drawing (“Jet Venturi Injector size B, Drawing number BA 2700-3, revision B”) was approved on 3/20/17 without your firm validating (or verified where appropriate) the change before your implementation.
On 2/5/20 (during the FDA inspection), your firm signed off on a test report (R20 001-00) for attaching the Jet Venture to the Universal Barrel with the ejector height change from (b)(4). The outcome of the test was no scraping or resistance during inserting and removing instruments (components) which was repeated multiple of times with combination of several different barrels and instruments. However, your firm failed to test the performance of your device under actual conditions of use or simulated use conditions in the actual or simulated environment in which the device is expected to be used. The safety and effectiveness of devices cannot be proven by final inspection and testing where a device may be rendered unable to properly perform and be unsafe and ineffective.
3) Failure to establish and maintain documented procedures for acceptance activities including inspections, tests, or other verification activities in order to verify that the specified requirements for the product are met, as required by 21 CFR 820.80(a). Specifically, procedure “QMS-016, Finished Product Release, version 3” states under section 3 that product release is the responsibility of QA where they need to “ensure the following before the finished product batch/lot is released:” “(b)(4).” During the time of this inspection, your firm provided our investigator with all available Assembly Inspection Reports for your Universal Barrel where several Universal Barrels failed for thread ((b)(4) for area of inspection) where the (b)(4). Your firm failed to check off the box that documents the part status as acceptable or rejected prior to release.
4) Failure to evaluate complaints to determine whether the complaint represents an event which is required to be reported to FDA under part 803, Medical Device Reporting, as required by 21 CFR 820.198(a)(3). Specifically, procedure QMS-021, “Adverse Drug Experience Reports and Medical Device Reports”, states under section 1 that “For each complaint, Quality Assurance must promptly evaluate the complaint to determine if the reported event or problem must be reported to FDA in an ADE Report or MDR.” “A decision tree will be completed to assist with the decision-making process”. “If the product is identified as a Medical Device, complete the MDR decision tree (FQMS-020).” Your firm failed to evaluate if Complaint BR-19-02, opened 11/1/2019 represented an event which is required to be reported as an MDR after your firm became aware that a 12/11 mm Tracheal tube broke away from its accessory fitting during the procedure. No MDR decision tree was completed to assist with the decision-making process.
In addition, your firm failed to evaluate if Complaint BR-19-01, opened 11/1/19 represents an event which is required to be reported as an MDR after your firm became aware that “the new barrel broke in the same manner as the previous” where “the tube coupling separated from the tube (Part # BT 2000)”. The complainant sent pictures of the defective barrel and your firm stated that they “understand what it is” and are sending them a “new replacement tube”. However, no MDR decision tree was completed to assist with the decision-making process where your firm documented the outcome of the injury or adverse event as being “no injury to the patient” even though your firm never evaluated if the patient or user were affected in anyway (e.g., injury, adverse event) since the box on the form was checked off as being “unknown/not reported”.
5) Failure to evaluate and investigate any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications, unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820.198(c). Specifically, your firm failed to follow “Complaint Handling and Investigation procedure” (“QMS-004, version 3”) which requires under section 2.6 “investigations should give consideration to the areas described below.” “Process or service and the nature of the complaint”; “Examination and evaluation of the retain sample, if appropriate”; “Examination and evaluation of the complaint sample, if available”; “Review of the batch record/device history file if lot number is known”; “Assessment of the trend of similar complaints”; “Assessment of the severity of the complaint (risks/impact)”; “Results should support the conclusion”; “CAPA assessment”. Section 8 also requires “complaints must be closed within (b)(4) after receipt”. For example:
On 11/7/19, your firm received a complaint (BR-19-03, part # 2410) concerning 2 rubbers (O-rings) coming off the universal barrel during sterilization. Your firm documented in your complaint file that there was no patient involved and investigation was pending (BD 2410). On 1/6/20, another complaint (BR-20-01) was filed from the same facility by email stating “I am reaching out again in regards to the rubbers for the universal barrel that we had issues with back in November”. “First, the facility wanted to know why the rubbers were coming off the barrel so easily and this time they weren’t cut like they were previously but I have 2 rubbers that should be attached to barrel but aren’t”. “It is unclear how the pieces are disconnecting from the scope”. “We do have procedures pending, so please advise on the best way to resolve this issue?” The complaint further documents that “two O-rings were found in sterilization tray, investigation pending (BD2410)” for two months after the initial complaint was received from your customer. In addition, your firm stated during the inspection “that the O-rings in the sterilization tray may not even belong to the universal barrel and he is waiting for the part to be returned”. Your firm must perform a complete investigation when your device fails to meet specifications (O-rings coming off the universal barrel during sterilization, and customer had procedures pending where they needed to resolve this issue).
6) Failure to establish and maintain purchasing documents (includes an agreement) that clearly describes or references the specified requirements, including quality requirements, for purchased or otherwise received product and services, as required by 21 CFR 820.50(b). Specifically, procedure “QMS-025, version 01” states under section 1.1 that “Quality agreements will be established with critical suppliers providing services (e.g., contract manufacturing organizations, contract testing laboratories, etc.)”. However, your firm stated during this current inspection that there was no quality agreement between Lymol Medical Corporation and J.R. Poirier Tool & Machine Co. (J.R.) who is the contract manufacture and critical supplier of all components for the Elite X Class Rigid Bronchoscope System. For example, on 12/27/16 the firm performed a “Supplier Evaluation Summary” for this contract manufacturer which documents they have a “quality program, however, it is noted that the quality program is not based on the framework of QSR (21 CFR Part 820).” “Supplier is supplying bronchoscopes as a device component; LYMOL performs final assembly at LYMOL site (manufacturing steps for finished device).” “Based on this assessment, the supplier may remain on the Approved Supplier List as provisional” but are also considered a “critical supplier” requiring a Quality Agreement. Your firm failed to ensure that purchased or otherwise received product or services conform to specifications since there was no agreement between both parties on the methods of quality assurance that will be used to decide the acceptability of product or services (Bronchoscope components).
7) Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, as required by 21 CFR 820.70(a). Specifically, your firm’s BD 2410 Universal Barrel I Assembly Procedure requires a Barrel Cap ((b)(4)) assembly ((b)(4)) by (b)(4) and then tightening the (b)(4) to about (b)(4) torque. However, during the FDA inspection an investigator observed an employee assemble a universal barrel (b)(4) and (b)(4) without measuring the torque. The employee stated that his firm would measure the torque using a gauge but does not use any equipment presently, adding that if they used a torque gauge it would require the gauge to be calibrated. Your firm failed to ensure that the assembly of your Universal Barrell conforms to your specifications. If any deviations occur from specifications, then the process control procedures must describe those controls necessary to ensure conformance.
8) Failure to establish and maintain procedures to ensure that DHRs for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the DMR, including the dates of manufacture, the quantity manufactured, the quantity released for distribution, acceptance records, primary identification label and labeling used for each production unit, and any unique device identifier (UDI) or universal product code (UPC), and any other device identification(s) and control number(s) used, as required by 21 CFR 820.184. Specifically, your firm has not established and maintain procedures to ensure that Device History Records for its Elite X Class Rigid Bronchoscope System were manufactured in accordance with a DMR, which includes the batch records with dates of manufacturer, labeling, and any unique device identifiers since 2016. For example, during the time of this inspection, your firm provided the FDA investigator with all available Assembly Inspection Reports for your Universal Barrel (part # BD 2410), Tracheal Tube (part # BT 2201), and Jet Venturi (part # BA 2700); however, these documents did not include batch records and labeling. In addition, your firm stated that they stopped filling out the Assembly Inspection reports last year (2019) for all other components of the bronchoscope system since there had not been any issues with the parts.
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, 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 corrected. Also, should FDA determine that your devices do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted. If you believe that your products are not in violation of the Act, please respond to FDA with your reasoning and any supporting information for our consideration.
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 have questions regarding any issues in this letter, please contact Compliance Officer, Robert J. Maffei at 973-331-4906 or at Robert.Maffei@fda.hhs.gov. Please send your reply electronically to Gina Brackett, Director of Compliance Branch, at firstname.lastname@example.org.
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.
Joseph Matrisciano, Jr.
Program Division Director
Office of Medical Device and Radiological Health