Mr. Michael Schlenk
- Curasan AG, Frankfurt Facility
- Issuing Office:
- Center for Devices and Radiological Health
10903 New Hampshire Avenue
Silver Spring, MD 20993
VIA UNITED PARCEL SERVICE
Mr. Michael Schlenk
Chief Executive Officer
Lindigstrasse 4, D-63801
Dear Mr. Schlenk:
During an inspection of your firm located in Frankfurt, Germany on May 8, 2017 through May 11, 2017 an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Cerasorb Dental, Cerasorb M Dental, Cerasorb Perio, Revios Implant System, IngeniOs HA (Osbone DENTAL), IngeniOs Beta-TCP Bioactive (Ceracell DENTAL), and Cerasorb Ortho Foam. 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 Dirk Büschgens, Quality Management Representative dated July 11, 2017 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 for validating device design as required by 21CFR 820.30(g).
Specifically, your firm’s Design Control Procedure, Document #FEI.102, Revision 2, states the validation of development is to ensure that the product fulfills the requirements for the intended use as far as is known. A review of the Design History File (DHF) of the Osbone Dental revealed that the DHF was completed in July 2009; however no design validation was conducted.
We reviewed your firm’s response and conclude that it is not adequate. The corrections involve revision to documentation and training of personnel; however, they do not describe systemic review of your firm’s existing products to ensure that adequate design validation procedures were implemented. Additionally, there is no specified verification of effectiveness of the corrective actions, including the updated procedures.
2. 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 has not established a manufacturing procedure for (b)(4) to produce the (b)(4) in the manufacturing of the IngeniOs HA-Synthetic Bone Particles.
We reviewed your firm’s response and conclude that it is not adequate. The corrections include revision to SOP P3. 229 ((b)(4)), an examination of other procedures, expansion of the device master record specifications, and training of relevant personnel. However, these corrections do not include verification of the effectiveness of the updates to procedures and training, nor is there a review of potential adverse events resulting from a lack of production procedures.
3. 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).
Specifically, your firm’s How to Handle Complaints Procedure, Document #QM3.102, Revision 1 does not require complaints to be evaluated to determine whether the complaint should be filed as a Medical Device Reporting (MDR) to the FDA. Eleven out of 11 complaints, sampled from records dated January 2016 to May 2017, lacked MDR evaluation.
We reviewed your firm’s response and conclude that it is not adequate. You provided updated complaint handling procedures, and a complaint handling form. To assess the effectiveness, it was confirmed that all procedures were updated, however, you did not evaluate the effectiveness of the updated procedures in assessing complaints for MDR reportability.
Our inspection also revealed that your firm’s 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. Significant violations include, but are not limited to, the following:
Failure to develop, maintain and implement written MDR procedures, required by 21 CFR 803.17. For example, during the inspection of your firm, it acknowledged not having written MDR procedures.
We reviewed your firm’s response dated July 11, 2017 and conclude that it is not adequate.
For example: After reviewing your firm’s MDR Procedure titled “Medical Device Vigilance and Reporting System QM3.103-01” dated June 1, 2017, the following issues were noted:
1. The procedure does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example:
a. The procedure includes definitions for the terms “MDR reportable event,” and “serious injury,” found in 21 CFR 803.3. The procedure omits definitions of the terms “become aware,” and “caused or contributed,” from 21 CFR Part 803.3. The exclusion of the definitions for these terms from the procedure may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
b. The definitions of the terms “malfunction,” and “serious injury,” and the definition for the term “reasonably suggests,” are not consistent with the definitions of the terms in 21 CFR 803.3 and 803.20(c)(1), respectively, and will not allow your firm to correctly identify complaints as reportable events.
2. The procedure does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
a. Although the procedure includes references to 30 day, 5 day reports, it does not specify calendar days and work days, respectively.
3. The procedure does not describe how your firm will address documentation and record- keeping requirements, including:
a. Documentation of adverse event related information maintained as MDR event files.
b. Information that was evaluated to determine if an event was reportable.
c. Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable.
d. Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
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 3540, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case # 534581 when replying. If you have any questions about the contents of this letter, please contact: Matthew Krueger at 301-796-5585.
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.
CAPT Sean M. Boyd, MPH, USPHS
Deputy Director for Regulatory Affairs Office of Compliance
Center for Devices and Radiological Health
3200 Chapel Hill-Nelson Blvd Suite 201
Research Triangle Park, NC 27709