- Tem Innovations GmbH
- Issuing Office:
- Center for Devices and Radiological Health
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||10903 New Hampshire Avenue|
Silver Spring, MD 20993
APR 21, 2015
VIA UNITED PARCEL SERVICE
Dr. Thomas Ebinger
Chief Executive Officer (CEO)
Tem Innovations GmbH
Martin-Kollar Strasse, 13
Dear Dr. Ebinger:
During an inspection of your firm located in Munich, Germany on 10/20/2014 through 10/22/2014, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures various Class II medical devices comprising the ROTEM delta Whole Blood Hemostasis System using Thromboelastometry for in vitro coagulation studies. 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 Dr. Thomas Ebinger, CEO, dated November 3, 2014 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 control product that does not conform to specified requirement, as required by 21 CFR 820.90(a).
For example: your firm received Non-Conformance Report (NCR) # 14-04893, dated 05/14/2014, regarding non-conforming Rotrol P diluent units, identified with lot # 41819801. The NCR was submitted for further investigation and corrective action. A checkbox on the NCR form indicated that the product is “not accepted” and must be disposed or reworked. However, there was no indication as to how the nonconforming product was disposed/segregated and no corrections and corrective actions were identified. Your firm continued to distribute these non-conforming products, and specifically shipped (b)(4) of Rotrol P diluent (lot # 41819801) to the U.S. agent/distributor on 09/15/2014 after becoming aware of the nonconformance of this Rotrol P diluent product and failed to document any reprocessing or concessions for these lots.
Your firm’s management explained that it is not performing any proactive field corrections on these non-conforming products. We note a “memo to file” regarding the "Distribution and Complaints of Rotrol P Lot # 41819801…”, where it states that (b)(4), Tem Systems discussed (b)(4) Tem Innovations. Based on the evaluation of the risks that were discussed during the July 3, 2014 Risk Management Meeting in Germany and the limited number of resources (i.e. Rotrol P) available in the US, it was determined that the risk to the customers was neglig[ible] and that products could be replaced as needed upon customer request.” As a result, Tem will replace the non-conforming products free of charge upon receiving customer complaints.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a new version of the standard operating procedure (SOP) (b)(4) and form for nonconforming report, (b)(4). The new versions adequately show the part disposition and all required actions and will prevent a repetition of this observation. However, your firm did not provide completed NCRs showing evidence of the corrections of the deficiencies of the identified nonconformities in NCR #14-04893. Also, your firm did not present a plan or provide documentation of a comprehensive retrospective review of nonconforming products to ensure all nonconforming reports were initiated and completed as required and that the nonconforming products were quarantined and/or discarded as required.
2. Failure to establish and maintain procedures for receiving, reviewing and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).
For example: your firm's "Customer Complaint" SOP (b)(4), states in part, "(b)(4)." Your firm did not follow or adhere to the requirements of this SOP, in that the (b)(4) categorized as Class 3 (b)(4).
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided a new version of the SOP which includes improved description of the process and responsibilities during the complaint closure. However, your firm did not provide evidence to document: (b)(4) listed Class 3 Complaints as a correction to this deficiency; it trained appropriate staff on the revised complaint handling procedure; it conducted a retrospective review of all complaints to ensure they were handled in a timely manner as required by the revised procedure; and that it considered a systemic corrective action to include a retrospective review of other procedures for handling complaints to ensure they meet regulatory requirements.
3. Failure to establish and maintain the requirements, including quality requirements, that must be met by suppliers, contractors, and consultants, as required by 21 CFR 820.50(a).
For example: Your firm's "(b)(4) documents that suppliers of important components, or a critical supplier, are to be audited (b)(4). Your firm's (b)(4), is classified as a critical supplier, but your firm does not perform audits of this supplier. Additionally, the supplier audit schedule documents that no supplier audit was performed (b)(4) interval.
We reviewed your firm’s response and conclude that it is not adequate. Your firm provided an updated supplier list/audit plan which distinguishes between suppliers of critical components not requiring audits and suppliers of critical components (b)(4) does not require audit to be performed. However, your firm’s (b)(4) does not distinguish between suppliers of critical components not requiring audits and suppliers of critical components “(b)(4). There is no indication that this SOP was revised or updated to reflect the changes made to the supplier list/audit plan indicated above nor does it specify to refer to this updated supplier list/audit plan to distinguish between suppliers of critical components requiring/not requiring audits (b)(4) years. In addition, your firm did not provide evidence that it trained employees on the revised SOP as it relates to the updated form.
4. Failure to establish 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, as required by 21 CFR 820.22.
For example: your firm's 2013-2014 internal audit schedules required that (b)(4) be internally audited on or before (b)(4). However, the 2013-2014 internal audit schedule documents that these audit categories were not internally audited until approximately eight months later on (b)(4).
We reviewed your firm’s response and conclude that it is not adequate. You indicate that the audit due dates (the planned year of the audit) are recorded electronically in the "date" column, but the audit number was also hand-written in the same column, which may have been misinterpreted as a date by the FDA investigator, believing the audit was performed late. Your firm provided an updated "Audit program, FoFP03-001-01-TS" form for 2015-2016 which includes a separate column for "Audit No." to avoid “misunderstanding”. However, your firm did not provide evidence that it trained employees on the revised SOP as it relates to the updated form. In addition, your firm did not indicate whether it retrospectively reviewed all other areas (b)(4) to be audited to ensure they were audited as required.
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.
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 (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. 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: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Inspections Support Branch, White Oak Building 66, Rm 2622, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #447892 when replying. If you have any questions about the contents of this letter, please contact: Daniel Dill at 301- 796-2875.
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.
Office of In Vitro Diagnostics and
Center for Devices and
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