Inspections, Compliance, Enforcement, and Criminal Investigations
CRS Medical Diagnostics, Inc. 21-Mar-08
Department of Health and Human Services
Public Health Service
Minneapolis District Office
March 21, 2008
RETURN RECEIPT REQUESTED
Refer to MIN 08 – 10
Robert S. Brewer
CEO and Chairman of the Board
CRS Medical Diagnostics, Inc.
6754 W. Beloit Road
West Allis, Wisconsin 53219-2068
Dear Mr. Brewer:
During an inspection of your firm located in West Allis, Wisconsin, on December 17 - 28, 2007, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Fibrin Analysis Catheter Testing Systems (FACTS). 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 are intended 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 (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
These violations include, but are not limited to, the following:
1. Failure to validate a process whose results cannot be fully verified by subsequent inspection and test as required by 21 CFR § 820.75(a). The sterilization process validation did not include any evaluation to show that devices are non-pyrogenic as stated in the product labeling. In addition, the validation failed to evaluate the sterile barrier (package) integrity to show that the package can withstand the rigors of the sterilization process.
2. Failure to provide adequate resources for performing management activities, work, assessment activities, and audits, which is required by 21 CFR § 820.20(b)(2). Management with executive responsibility has not ensured that adequate resources and trained personnel are available to define, document, and implement a Quality System that meets the requirements of 21 CFR Part 820.
3. Failure to define the type and extent of control to be exercised over services and contractors as required by 21 CFR § 820.50(a)(2). There are no procedures requiring any review of documentation or any other means of verification that finished devices received from your kit packer have been subjected to the sterilization process.
4. Failure to establish, document, and implement procedures to control the design process for the device, which is required by 21 CFR § 820.30(a). There were no procedures for control of design activities such as design input [21 CFR § 820(c)], design output [21 CFR § 820(d)], design review [21 CFR § 820(e)], design verification [21 CFR § 820(f)], design validation [21 CFR § 820(g)], and design transfer [21 CFR § 820(h)] for the FACTS.
5. Failure to maintain a design history file, as required by 21 CFR § 820.30(j), to demonstrate that the design was developed following an approved design plan and the design control requirements of 21 CFR § 820. Specifically, the design history file for the FACTS fails to demonstrate that the device design and subsequent design changes were conducted following any defined or documented design plan or procedures.
6. Failure to include or refer to the location of all specifications in the device master record, as required by 21 CFR § 820.181(a). For example, the device master record (provided for review by the contracted kit packer) is incomplete in that only one size fibrin testing brush size (Orange Collar) is identified. There is no reference to the other size fibrin brushes that are manufactured and distributed. Also, your firm does not maintain a copy of the device master record, and the device master record is incomplete in that component and material requirements and specifications were not accessible.
7. Failure to establish complete corrective and preventive action (CAPA) procedures addressing the analysis of sources of quality data to identify existing and potential causes of nonconforming product or other quality problems, which is required by 21 CFR § 820.100(a)(1). CAPA procedures fail to identify the potential sources of quality data to be investigated and evaluated for potential CAPA actions. For example, there are no procedures for handling nonconforming product that may be detected internally, or upon return to the inspected firm after being placed into commercial distribution.
8. Failure to establish procedures addressing verification or validation of corrective and preventive actions as required by 21 CFR § 820.100(a)(4). CAPA procedures do not require verification or validation (where appropriate) to ensure that the action is effective and does not adversely affect the finished device.
9. Failure to establish complaint handling procedures that ensure that all complaints are evaluated to determine whether the complaint should be filed as a Medical Device Report (MDR). This is required by 21 CFR § 820.198(a)(3). Specifically, customer complaint handling procedures fail to address the need to evaluate complaints for MDR reportability.
10. Failure to establish procedures for management review of the quality system, and failure to conduct management reviews as required by 21 CFR § 820.20(c).
11. Failure to establish procedures for conducting quality audits, and failure to conduct quality audits as required by 21 CFR § 820.22.
12. Failure to establish document control procedures, which is required by 21 CFR § 820.40. There are no procedures governing the creation, approval, or control of any Quality System documents.
13. Failure to establish procedures to ensure that device history records for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record and the Quality Systems regulation as required by 21 CFR § 820.184. Specifically, there are no procedures directing the creation or maintenance of device history records, and no device history records were available for review.
Additionally, during our post-inspection review of your promotional brochures for the FACTS device, we observed that these brochures contain the statement “FDA approved.” However, your device has not received approval from the FDA. The FACTS device is marketed under a premarket notification [510(k)]). Under 21 CFR § 807.97 (“Misbranding by reference to premarket notification”), “[a]ny representation that creates an impression of official approval of a device because of complying with the premarket notification regulations is misleading and constitutes misbranding.”
You 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/or civil money penalties. Also, federal agencies are advised of the issuance of all 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 15 working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
Your response should be sent to Timothy G. Philips, Compliance Officer, at the address on this letterhead. If you have any questions about the content of this letter please contact Mr. Philips at (612) 758-7133.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483, issued at the conclusion of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.
W. Charles Becoat