Inspections, Compliance, Enforcement, and Criminal Investigations
Osmed GmbH 11/18/11
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
NOV 18 2011
VIA UNITED PARCEL SERVICE
Mr. Michael Kircheisen
D-98693 llmenau, Germany
Dear Mr. Kircheisen:
During an inspection of your firm located in llmenau, Germany, on July 25, 2011, through July 28, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Osmed Hydrogel Tissue Expander. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321 (h), this product is a device because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.
This inspection revealed that this device is 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, its 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.
Your firm's response to the Form FDA 483 (FDA 483) received September 12, 2011, was not reviewed because it was not received within fifteen business days of issuance. The response may be evaluated along with any other written material provided in response to the violations cited in this Warning Letter. These violations include, but are not limited to, the following:
1. Failure to ensure that 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:
• Process validation has not been performed for the (b)(4) that demonstrates the reproducibility of the process, especially during the worst case process conditions and the acceptable process parameter range. (b)(4) In addition, the parameters in the validation are not the same parameters used during manufacturing.
2. Failure to establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met, as required by 21 CFR 820.75(b). For example, (b)(4) is not subject to a routine testing schedule for microbiological or endotoxin levels.
3. Failure to establish and maintain adequate procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a). For example, (b)(4)
4. Failure to adequately maintain complaint files, as required 21 CFR 820.198(a). For example, the complaint file from one of the complaints of the log sheet could not be located.
5. 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, (b)(4)
6. Failure to establish and maintain procedures to ensure that DHRs (device history records) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the DMR (device master record) and the requirements of this part, as required by 21 CFR 820.184. For example, (b)(4). There is no documentation of the ultimate disposition of the retained products in the DHR.
During the inspection FDA also found that you are exporting and providing labeling for the Osmed Hydrogel Tissue Expander to the United States that suggests the use of the device in the head, mouth, trunk, and extremities without the required marketing clearance or approval, in violation of the Act.
Our inspection revealed that the Osmed Hydrogel Tissue Expander is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351 (f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g).
The Osmed Hydrogel Tissue Expander is also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because you did not notify the Agency of your intent to introduce the device into commercial distribution in that a notice or other information regarding the new intended use of the device was not provided to the FDA, as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 CFR 807.81 (a)(3)(ii). Specifically, the Osmed Hydrogel Tissue Expander was cleared under K010852 for the following indication: "[f]or the facilitation of normal growth of orbital soft tissues and bone to achieve proximate facial symmetry in congenital anophthalmos and microphthalmos."
For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. [21 CFR 807.81(b)] The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.
A follow up inspection will be required to assure that corrections and/or corrective actions are adequate.
Given the serious nature of the violations of the Act, the hydrogel tissue expanders manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381 (a), in that they appear to be adulterated. As a result, FDA may take steps to refuse these products, known as "detention without physical examination," until these violations are corrected. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violations described in this letter. We will notify you if your firm's response appears to be adequate, and we may need to re-inspect your firm's facility to verify that the appropriate corrections and/or corrective actions have been made.
Also, 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 actions (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 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #232556 when replying. If you have any questions about the contents of this letter, please contact: Ronald Swann at 301-796-5770.
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 lnspectional 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