Department of Health and Human Services
|Public Health Service
Food and Drug Administration
|New England District Office
One Montvale Avenue, 4th floor
Stoneham, MA 0210
CMS # 445589
UNITED PARCEL SERVICE
December 8, 2014
Chairman of the Board
Karl Storz GmbH&Co.
Baden-Wurrtemberg 78532 Germany
Bruce Watkins, General Manager
Karl Storz Endovision, Inc.
91 Carpenter Hill Road
Charlton, MA 01507-5274
Dear Ms. Storz and Mr. Watkins:
The Food and Drug Administration (FDA) conducted an inspection of your firm’s medical device operation at Karl Storz Endovision, Inc., Charlton, MA, from October 14 through 29, 2014. During the inspection, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures endoscopes, including the Flex-X2 Flexible Ureteroscope. 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 your response dated November 20, 2014 which responded to the Form FDA 483, List of Inspectional Observations issued to your firm on October 29, 2014. Our comments regarding the adequacy of your response are described below.
Your significant violations are as follows:
1. Failure to establish and maintain design validation procedures to ensure that the device conforms to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions; and to ensure the results of design validation, including the identification of the design, methods, the date, and the individuals performing the validation are documented in the design history file, as required by 21 CFR 820.30(g). During the inspection, your firm did not have any design validation data to demonstrate that the cleaning brush specified in the Instruction Manual is appropriate for the Flex-X2 Flexible Ureteroscope, Model #112781AU1.
We understand that you will be conducting a design review of all your endoscopes to ensure that the cleaning brushes specified in the instruction manuals are appropriate for each of your endoscopes. We also note that you will be performing additional cleaning validations in response to FDA-483 observation #1. These corrective actions appear adequate to address the violation. In response to this Warning Letter, please provide us with a summary of your design review when completed and an updated list of all endoscopes referencing the date cleaning validation was completed.
2. Failure to establish and maintain procedures for verifying or validating corrective and preventive actions, to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4). For example:
· CAPA #1010 was opened on August 28, 2013 to address complaints with cleaning brushes not being able to fit properly into the working channel of endoscopes. The root cause investigation noted that the (b)(4) cleaning brush is not included with the Flex-X2 Ureteroscope, model # #11278AU1. This CAPA was closed on September 12, 2013 without ensuring the appropriate brush is referenced properly in the future for all affected models.
· CAPA #1012 was opened on August 28, 2013 to verify process control parameters utilized in your Shaft Composite Assembly Procedure, specifically the (b)(4) process. Your firm’s corrective action was to perform an operational qualification, OQ-393-13, to establish the appropriate oven settings. Data provided in OQ-393-13 noted that (b)(4) replicates failed your peel force acceptance criteria of (b)(4). The report indicated that an external factor may have led to the failures, but no additional explanation was provided. This CAPA #1012 was closed on November 26, 2013 and referenced OQ-393-13 as documentation of effectiveness.
Your response is not adequate to address this violation. In response to the Warning Letter, you should provide us with a description of the steps you are taking to update your CAPA verification activities to ensure that the corrective actions you implement are effective for all new CAPA’s. You should also provide evidence to demonstrate that verification activities were properly conducted for previously closed CAPA’s.
3. Failure to develop, conduct, control and monitor production processes to ensure that a device confirms to its specifications, as required by 21 CFR 820.70(a). For example, during the inspection, we witnessed cleaning operations being conducted on returned endoscopes in your evaluation center and observed the following:
· A reference document posted and utilized by employees in the cleaning / high level disinfection area did not reference the appropriate brush models (as specified in EV009), to be used when cleaning the endoscopes.
· On October 17, 2014, our investigator observed your operator did not use the specified brush for cleaning the intubation scope, Model (b)(4) and the brush did not fit through the working channel. The device was subsequently processed through the decontamination station and associated paperwork was stamped “Decontaminated”.
Your response appears adequate to address this violation. In response to the Warning Letter, you should provide us with copies of your associated CAPA’s when all verification activities have been demonstrated to be effective and the CAPA’s have been closed. You should also provide evidence to demonstrate that all associated training CAPA’s have been completed.
4. Failure to review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications, as required by 21 CFR 820.198(c). For example:
· Complaint #(b)(4) received on September 16, 2014 noted that a small white foreign body was observed in the kidney during a stone removal procedure. It also noted that the endoscope was missing a small white piece from the tip. As of October 29, 2014, your investigation of this complaint did not include a review of the device history record for the device, as required by your complaint procedure, QP042.
· Complaint #(b)(4) received on August 11, 2014 referenced a problem with the cleaning brush. Your investigation for this complaint did not reference a similar defect trend found in your 2013 CAPA #1010. This specific CAPA was closed on September 12, 2013 but noted that it should be referenced for any future complaints involving a cleaning brush issue.
Your response is not adequate to address this violation. In response to the Warning Letter, you should provide us with confirmation when all of your complaint evaluations have been completed. You should also provide evidence to demonstrate that verification activities were properly conducted for all associated CAPA’s related to your complaint system.
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 (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.
Please send your reply to the Food and Drug Administration, Attention: Karen N. Archdeacon, One Montvale Avenue, Stoneham, MA 02180. If you have questions regarding any issues in this letter, please contact Ms. Archdeacon at 781-587-7491.
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.
Mutahar S. Shamsi
New England District Office
Cc: Karl – Christian Storz, President
Karl Storz GmbH&Co.
Baden-Wurrtemberg 78532 Germany
Serkan Sezer, VP Global Quality Management & Regulatory Affairs
Karl Storz Endoscopy-America, Inc. (KSEA)
2151 E. Grand Avenue
El Segundo, CA 90245
Gary Macker, VP of North America Operations
Karl Storz Imaging, Inc.
175 Cremona Drive
Goleta, CA 93117