Inspections, Compliance, Enforcement, and Criminal Investigations
Grimm Scientific Industries 6/19/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Cincinnati District Office
June 19, 2012
Joseph E. Grimm
Grimm Scientific Industries
1403 Pike Street
Dear Mr. Grimm:
During an inspection of your firm located in Marietta, Ohio, on February 27, 2012, through March 2, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the CRYOTherm, CRYOPress, and PARATherm 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.
Our inspection revealed that your firm markets the CRYOTherm, Model 4812 Heat Pump and Model 4802 Chiller. This device differs from your firm’s previously cleared device (K864721) because it includes thermostatically-controlled heating and cooling and incorporates changes in the user interface. These modifications have the potential to significantly change the performance characteristics and specifications of the cleared device. Regulations at Title 21, Code of Federal Regulations (CFR), Part 807 require a cleared application under section 510(k) of the Act, 21 U.S.C., § 360(k), for any change that “could significantly affect the safety or effectiveness of a device.” See 21 CFR 807.81(a).
Therefore, the CRYOTherm, Model 4812 Heat Pump and Model 4802 Chiller 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 device is also misbranded under section 502(o) the Act, 21 U.S.C. 352(o), because your firm did not notify the agency of its intent to introduce the device into commercial distribution, as required by section 510(k) of the Act. 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 its device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether your firm’s product may be legally marketed.
This inspection also 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. We received a response from you dated March 12, 2012, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations (FDA 483) that was issued to you. 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 finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820.80(d). Specifically;
a. There is no written finished device acceptance procedure for the CRYOTherm, single or dual, hydrotherapy device.
b. Twelve CRYOTherm acceptance records reviewed did not include the signature and date authorizing release of the device for distribution.
c. A total of 4 out of 12 CRYOTherm acceptance records reviewed did not document that the device passed test requirements used to determine acceptance of the device.
The response dated March 12, 2012, is not adequate. Your response states that the method used for finished device acceptance will be formalized, standardized, and established. However, neither a copy of this new procedure, nor a timeframe for its completion was provided. Additionally, you did not indicate that all 12 finished device acceptance records would be reviewed and signed as required; that a correction would be implemented for the devices that did not meet finished acceptance criteria; and that a review of all other acceptance activities would be performed to ensure that they were completed as required.
2. 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, a total of 3 out of 12 acceptance records reviewed for the CRYOTherm devices had an out-of-specification psi for adjusting the superheat; and 1 of the 12 did not have testing documented. These devices were not handled as non conformances and were still distributed.
The response dated March 12, 2012, is not adequate. Your response states that specifications will be reviewed to ensure that they properly describe the critical criteria, and that tolerances will be added to these specifications, where appropriate, to clarify requirements. However, a copy of the new criteria was not provided, nor did your response address how you will ensure that all established criteria will be met. Additionally, your response did not indicate how devices that did not meet specifications but were already distributed will be handled, nor did it demonstrate that all acceptance records were reviewed to ensure that no other nonconforming products have been distributed.
3. Failure to establish and maintain adequate procedures for implementing corrective and preventive actions, as required by 21 CFR 820.100(a).
Specifically, your firm’s “Corrective Action Procedure,” 14.0, Rev 0, and “Preventive Action Procedure,” 14.1, Rev 0, both dated 11-20-09, do not address how data sources will be analyzed to identify existing and potential causes of nonconforming product; verifying or validating the corrective action to ensure that it is effective and that it does not adversely affect the finished device; nor do these procedures address documenting all corrective and preventive action activities. In addition, for the 10 corrective actions reviewed, verifications and/or validations were not performed and the investigations were not documented. For example, investigations and verification/validation activities were not documented for corrective action #59 (issued for CRYOTherm suction temperatures over 65F) and #146 (issued for PARATherm microprocessing boards failing in process); however, these corrective actions were still implemented.
The response dated March 12, 2012, is not adequate. Your response states that the corrective and preventive action procedures will be revised to describe in more detail how data is received and analyzed in order to identify existing and potential causes of nonconformities and address the need for verification and/or validation. However, you did not provide these revised procedures, nor did you address documenting activities and completing verification and/or validation for the 10 corrective actions implemented. Additionally, your response did not address reviewing all corrective actions to ensure that investigations, and verifications and/or validations were documented.
4. Failure to establish and maintain adequate 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). Specifically;
Your “Engineering Change Order” procedure 5.1, Rev 0, dated 7-25-09, does not address verifying and/or validating design changes. In addition, four of the design changes and four of the corrective action design changes reviewed have not been verified and/or validated.
The response dated March 12, 2012, is not adequate. Your response states that the “Engineering Change Order” procedure will be revised to give guidelines as to when verification and/or validation are required and that this is documented. However, you did not provide this revised procedure, nor does the response address completing verification and/or validation activities for the eight design changes implemented. Additionally, you did not indicate that other changes would be reviewed to ensure they are documented as corrective actions; nor did you state that all changes would be reviewed, as a systemic corrective action.
5. Failure to establish and maintain adequate installation and inspection instructions and, where appropriate, test procedures that include directions for ensuring proper installation, so that the device will perform as intended after installation, as required by 21 CFR 820.170(a). Specifically;
There are no written installation procedures for the CRYOTherm devices that are installed by your firm; and the installation and testing performed is not documented.
The response dated March 12, 2012, is not adequate. Your response states that a new procedure for installation, inspection, and testing instruction will be written for inclusion in the Quality Procedure Manual. However, you did not provide a copy of the new installation procedure, nor a timeframe for its completion. Additionally, you did not indicate that all products installed would be reviewed to ensure that they were installed as required.
6. Failure to adequately review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications, unless such investigation has already been performed for another complaint and an investigation is not necessary, as required by 21 CFR 820.198(c). Specifically;
Your “Customer Complaint Procedure,” dated 11-20-09, does not address investigating complaints involving the possible failure of a device. In addition, a total of 12 out of 21 customer complaints reviewed did not have a documented failure investigation, nor was there a statement indicating that another investigation for a similar complaint was already performed and that an investigation was not necessary. For example, Complaints #686 and #912 were opened for “Water Cloudy” and “Cold tank frozen over.” Your firm sent replacement filters to the customers; however, there was no investigation documented into why the filters needed to be changed.
The response dated March 12, 2012, is not adequate. Your response states that a review of the existing complaint procedure will be conducted and that revision will be made, as necessary. However, neither the revised complaint procedure, nor a timeframe for its completion was provided. Additionally, your response did not address conducting investigations for the 12 customer complaints listed, nor that all complaints would be reviewed to determine whether investigations had been conducted and documented.
7. Failure to establish and maintain procedures for acceptance of incoming product, as required by 21 CFR 820.80(b). Specifically;
Your firm does not have an established procedure to address incoming acceptance activities. According to you, your firm uses the procedure 13.0, “Control of Nonconforming Products” for handling incoming inspection of components; however, this procedure does not explain that it is to be used for incoming inspection.
The response dated March 12, 2012, is not adequate. Your response states that an Incoming Inspection Procedure will be documented, explained, and implemented. However, neither the new procedure, nor a timeframe for its completion was provided. Additionally, your response did not indicate that all parts and components received would be reviewed to ensure that they were received as required and according to the new procedure.
8. Failure to establish procedures for quality audits, to 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.
The adequacy of the response dated March 12, 2012, cannot be determined at this time. Your response states that Internal Quality Audits have been conducted and that a Quality Audit procedure will be written and included in the Quality Procedure Manual. However, neither a copy of this procedure, nor the timeframe of its completion were provided.
Our inspection also revealed that your 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 (MDR) regulation. Significant deviations include, but are not limited to, the following:
Failure to develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17. For example, your firm’s MDR procedure titled “Quality Procedures, Customer Complaint Procedure Number: 25.0, Revision 0, Issue Date: 11-20-09,” does not establish a process that meets the requirements of 21 CFR 803.17.
The adequacy of the response dated March 12, 2012, cannot be determined at this time. Your firm states that a separate Medical Device Reporting Procedure will be written and added to the Quality Procedure Manual. However, your firm did not provide the new procedure, nor did it provide a timeframe for its completion.
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 Food and Drug Administration 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.
We are requesting that you submit to this office, according to the schedule below, certification by an outside expert consultant that he/she has conducted an audit of your establishment's manufacturing and quality assurance systems relative to the requirements of the device quality system regulation (21 CFR Part 820). You should also submit a copy of the consultant's report, and certification by your establishment's Chief Executive Officer (if other than yourself) that he or she has reviewed the consultant's report and that your establishment has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections should be submitted to this office by the following date:
• Initial certifications by consultant and establishment – January 1, 2013.
Please notify this office in writing within fifteen working days from the date you receive this letter of the specific steps that 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: Ms. Gina Brackett, Compliance Officer, Food and Drug Administration, 6751 Steger Drive, Cincinnati, Ohio 45237. If you have any questions about the content of this letter please contact Ms. Brackett at (513) 679-2700, ext. 2167, or by facsimile at (513) 679-2773.
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 FDA 483 issued at the closeout 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.
Paul J. Teitell