Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
White Oak Building 66
Silver Spring, MD 20993
November 22, 2013
VIA UNITED PARCEL SERVICE
President, Owner and General Manager
Dear Mr. Tröndle:
During an inspection of your firm located in Geisingen, Germany, on June 24, 2013, through June 27, 2013, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures an Intraluminal Artery Stripper, Morcellator, Electrosurgical, Cutting & Coagulation & Accessories, Laparoscope, and General & Plastic Surgery devices. 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 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 July 17, 2013, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which 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 to ensure, 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: CAPA 2333, dated March 21, 2013, was opened to identify and address manufacturing processes requiring validation according to your firm’s Validation Master Plan, dated March 25, 2013. The Validation Master Plan requires (b)(4) manufacturing processes to be validated. CAPA 2333 shows that (b)(4) out of the (b)(4) processes requiring validation, including (b)(4) and (b)(4), have not been validated. This was identified as an issue by your firm as far back as (b)(4), according to CAPA 2333.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a summary and copies of the work instructions applicable to the processes that require validation as well as a copy of the Master Validation Plan. However, your firm did not provide copies of the individual protocols for the processes, which remain to be validated, to determine whether these are technically adequate. Your firm states that it projects all of the validations will be completed by December 2013.
2. Failure to validate computer software for its intended use according to an established protocol when computers or automated data processing systems are used as part of production or the quality system, as required by 21 CFR 820.70(i). For example: Document No. IN-26_01_002, No. 1, dated March 25, 2013, Validierungsmasterplan [Validation Master Plan] developed as part of CAPA 2335, states that (b)(4), (b)(4), and (b)(4), are software programs that are considered critical, which requires software validation. These programs have not been validated by your firm.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a copy of its validation matrix, which documents the need to validate the software processes used at the facility. Also, your firm provided documentation of the validation steps completed. However, your firm did not provide copies of the individual protocols for the processes, which remain to be validated to determine whether these are technically adequate. Your firm states that it projects all of the validations will be completed by December 2013.
3. Failure to establish and maintain procedures for the identification, documentation, validation or, where appropriate, verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). For example: Procedure No. P2-12-00, dated June 27, 2008, Forschung & Entwicklung [Research & Development], states that the (b)(4) of the Final Design Review. However, the (b)(4) were finalized prior to the final Design Review. Projektreview 03 [Design Review 3] ended on April 10, 2013, and (b)(4) has a date of December 3, 2012, (last updated on March 8, 2013), which is prior to the Final Design Review date of April 10, 2013.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a copy of its revised design control procedure, P2-12 Forschung & Entwicklung [Research and Development]. This procedure indicates that product (b)(4) are developed at each of the design and development phases to verify the design and that these are not considered final (b)(4). However, your firm did not provide a copy of the design change procedure and other documentation as applicable to demonstrate that the design change requirements were met.
4. Failure to establish and maintain procedures to control all documents that are required by 21 CFR 820, as required by 21 CFR 820.40. For example: The Quality Manager/Quality Representative stated that all actions for CAPA 1716 and CAPA 2339 had been completed by March 30, 2013, and July 11, 2011, respectively, although they were not finalized within the (b)(4) software system until June 23, 2013. Additionally, an uncontrolled printout (hardcopy) of Test report 2011-02-23_UB dated February 23, 2011, was initiated by the R&D Manager during the inspection in June 2013 because it did not have approval signatures.
Your firm’s response to this observation appears to be adequate. Your firm provided a copy of new work instructions, AA-23_00_004 Erfassung einer CAPA [Documenting a CAPA], which describe the steps that need to be followed to adequately document a CAPA in the (b)(4) system. Your firm states that training was not required because the process developer is also the owner for CAPA activities and no other employee is affected. Additionally, your firm provided a copy of the document control procedure, P3-07_02 Informations-und Datenmanagement [Management of Information and Data], which defines the requirements that apply to documents subject to document control procedures, including quality records. The procedure provides a process for document approval, document storage, and identification and segregation of obsolete documents. Further, it specifies that records maintained electronically are effective only in the electronic version. Lastly, your firm provided a copy of training records dated July 8 and 9, 2013, of those employees authorized to handle documents and records.
5. Failure to establish and maintain procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system. These quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited, as required by 21 CFR 820.22. For example: the audit plan updated on (b)(4), for (b)(4) executed internal quality audits and (b)(4) scheduled audits, shows that (b)(6), Security Officer for Medical Devices, audited the following: Auditprozess/Internes Audit in (b)(4) & (b)(4), Riskomanagement in (b)(4) & (b)(4), Meldesystem [Medical Device Reporting], in (b)(4) & (b)(4), QA/Fertigungsuberwachung [Production Control] in (b)(4) & (b)(4), QA/Lenkung Fehlerhafter Produkte [Control of Nonconforming Product] in (b)(4) & (b)(4), QM system/Managementsystem in (b)(4), (b)(4) & (b)(4), and Informationsmanagement in (b)(4), (b)(4), & (b)(4). Additionally, he was scheduled to perform the majority of the items listed above for (b)(4). Per his job description, the Security Officer for Medical Devices is directly responsible for the functions he audited in (b)(4), (b)(4), and (b)(4).
The adequacy of your firm’s response cannot be determined at this time. Your firm states that as of June 1, 2013, a new employee was hired to fulfill the title of Technical Manager for Production Control in the areas of machining, equipment maintenance, production planning, and assembly. Additionally, your firm states that the new employee will be responsible for conducting internal quality audits in the areas not directly under his responsibility, after he completes Trokamed’s quality system training. Your firm provided a copy of the new employee’s quality auditor certificate. However, your firm did not provide a copy of training records and copies of executed quality audits demonstrating that those conducting the audits, since the completion of the inspection, do not have direct responsibility for the materials being audited. Your firm plans to submit additional supporting information in November 2013.
U.S. 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 deviations 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, including 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 action (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. Please provide a translation of documentation not in English to facilitate our review.
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Operations Branch, White Oak Building 66, Rm 2622, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #414184 when replying. If you have any questions about the contents of this letter, please contact: Daniel Walter, Vascular and Circulatory Support Devices Branch Chief, Tel: 301-796-5587 or Fax: 301-847-8138.
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.
Steven D. Silverman
Office of Compliance
Center for Devices and